Full Text Available Abstract Background β2-adrenoceptor (β2AR genepolymorphism glutamine 27 glutamic acid (Gln27Glu and Arg16Gly were reported to have an association with obesity and obesity related disorders in some population. We evaluated Gln27Glupolymorphism in the β2AR gene in obese Saudi populations to investigate the association of β2AR gene with obesity and other related metabolic parameters. Design We studied possible association of Gln27Glu in β2AR gene with body mass index (BMI, anthropometric measurements and other metabolic parameters. The β2AR genepolymorphism (Gln27Glu was identified by sequencing PCR products representing locus of interest. Based on BMI, the subjects were divided into three groups, normal weight, overweight and obese. The genotype and allele frequency were calculated separately for each group. Results The allelic frequency of Glu27 did not differ amongst the three groups, though the Glu27 homozygote (Glu/Glu were more in obese subjects and had higher concentration of triglyceride, leptin and insulin compared to in the Gln27 heterozygotes and Gln/Gln homozygotes. Conclusions In this study we were able to provide evidence on the influence of Gln27Glu genetic variant of β2AR gene on lipid phenotypes, insulin and leptin levels in the Saudi populations.

Full Text Available BACKGROUND: The beta2-adrenergic receptor (ADRB2 genepolymorphism has been implicated in susceptibility to obesity, but study results are still controversial. OBJECTIVE: The present meta-analysis is performed to determine whether there are any associations between the Gln27Glu (rs1042714 or the Arg16Gly (rs1042713 polymorphisms in ADRB2 and obesity susceptibility. METHODS: The PubMed (1950-2014, Embase (1974-2014, and China National Knowledge Infrastructure (CNKI, 1994-2014 databases were searched using the search terms ("Beta2-adrenergic receptor", "β2-adrenergic receptor" or "ADRB2", "polymorphism," and "obesity". Fixed- or random-effects pooled measures were determined on the bias of heterogeneity tests across studies. Publication bias was examined by Egger's test and the modified Begg's test. RESULTS: Eighteen published articles were selected for meta-analysis. Overall analyses showed that rs1042714 (Gln27Glu was associated with significantly increased obesity risk in the heterozygote model (Gln/Glu vs. Gln/Gln: OR: 1.16, 95% CI: 1.04-1.30, I2 = 49%, P = 0.009 and the dominant model (Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00-1.44, I2 = 55%, P = 0.04, whereas no significant association was found in the other models for rs1042714. Also, no significant association was found between the rs1042713 (Arg16Gly genepolymorphism and the risk of obesity in all genetic models. In addition, neither rs1042713 (Arg16Gly nor rs1042714 (Gln27Glu showed any significant association with obesity susceptibility when the population were stratified based on gender. CONCLUSION: Our meta-analysis revealed that the rs1042714 (Gln27Glupolymorphism is associated with obesity susceptibility. However, our results do not support an association between rs1042713 (Arg16Gly polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by more case-control and cohort studies.

Full Text Available Objectives: This study aimed to assess the distribution of missense mutations in the adrenoceptor β2 (ADRB2 gene in an Omani cohort. Methods: This study was carried out between May 2014 and March 2015 at the Sultan Qaboos University, Muscat, Oman. Blood samples were taken from 316 unrelated Omani subjects. Genotyping for rs1042713 (c.46A>G, p.Arg16Gly, rs1042714 (c.79C>G, p.Gln27Glu and rs1800888 (c.491C>T, p.Thr164Ile polymorphisms was performed by real-time polymerase chain reaction using single nucleotide polymorphism (SNP genotyping assays. The allelic frequencies of these polymorphisms were estimated on the basis of the observed numbers of specific alleles from the genotype data for male and female subjects. The genotype frequencies for each polymorphism were tested for deviation from the Hardy-Weinberg equilibrium. Results: Gly16 and Glu27 were the most frequent variants found among the cohort (63% and 75%, respectively. The Ile164 variant was not detected in the study population. There was a significant linkage disequilibrium between the rs1042713 and rs1042714 SNPs (r2 = 0.209; P ≤0.001. The most observed haplotypes were Gly16-Gln27 and Arg16-Gln27 (0.37 and 0.38, respectively. The frequency of Gly16-Glu27 was 0.25, comprising all Glu27 carriers. Conclusion: The allelic distribution of variants in this Omani cohort was similar to distributions reported among Caucasian populations.

The β-2 and β-3 adrenergic receptors (ADRB2 and ADRB3) are thought to play a role in energy expenditure and lipolysis. However, the effects of the ADRB2 glutamine (Gln) 27 glutamic acid (glutamate) (Glu) and ADRB3 tryptophan (Trp) 64 arginine (Arg) polymorphisms on weight loss remain controversial. The aim of this study was to investigate the effect of these polymorphisms on changes in weight and body composition during a controlled weight-loss program. One hundred seventy-three healthy overweight and obese participants (91 women, 82 men) aged 18-50 years participated in a 22-week-long intervention based on a hypocaloric diet and exercise. They were randomly assigned to 1 of 4 groups: strength, endurance, strength and endurance combined, and physical activity recommendations only. Body weight, body mass index (BMI), and body composition variables were assessed before and after the intervention. Genetic analysis was carried out according to standard protocols. No effect of the ADRB2 gene was shown on final weight, BMI, or body composition, although in the supervised male group, Glu27 carriers tended to have greater weight (p = 0.019, 2.5 kg) and BMI (p = 0.019, 0.88 kg/m(2)) reductions than did noncarriers. There seems to be an individual effect of the ADRB3 polymorphism on fat mass (p = 0.004) and fat percentage (p = 0.036), in addition to an interaction with exercise for fat mass (p = 0.038). After the intervention, carriers of the Arg64 allele had a greater fat mass and fat percentage than did noncarriers (p = 0.004, 2.8 kg). In conclusion, the ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms may influence weight loss and body composition, although the current evidence is weak; however, further studies are necessary to clarify their roles.

...) polymorphisms on weight loss remain controversial. The aim of this study was to investigate the effect of these polymorphisms on changes in weight and body composition during a controlled weight-loss program...

Full Text Available Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ genepolymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01 were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01. However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55. Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels.

Our aim was to evaluate the influence of the Gln27Glupolymorphism of the β2-adrenergic receptor (ADRβ2) gene, fat intake and physical activity on the energy expenditure (EE) and nutritional status of obese women. Sixty obese women (30-46 years) participated in the study and were assigned to three groups depending on the genotypes: Gln27Gln, Gln27Glu and Glu27Glu. At baseline and after nutritional intervention, the anthropometric and body composition (bioelectrical impedance), dietary, EE (indirect calorimetry) and biochemical variables were measured. All women received a high-fat test meal to determine the postprandial EE (short-term) and an energy-restricted diet for 10 weeks (long term). The frequencies of Gln27Gln, Gln27Glu and Glu27Glu were 36.67, 40.0 and 23.33 %, respectively. Anthropometric and biochemical variables and EE did not differ between groups, although women who had no polymorphism demonstrated decreased carbohydrate oxidation. On the other hand, the Glu27Glu genotype showed a positive relation with EE in physical activity and fat oxidation. The environmental factors and Gln27Glupolymorphism did not influence the nutritional status and EE of obese women, but physical activity in obese women with the polymorphism in the ADRβ2 gene can promote fat oxidation. The results suggest that encouraging the practice of physical exercise is important considering the high frequency of this polymorphism in obese subjects.

Full Text Available The individual response to diet may be influenced by genepolymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713, ADRB3 (Trp64Arg, rs4994 and GHRL (Leu72Met, rs696217 polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109. The body mass index (BMI was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 x 2 were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES. The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001, for high and low SES (p < 0.05 and mainly for participants with 30-49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glupolymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018 and the 30-39 y (p = 0.036 groups, suggesting a role for this polymorphism related to BMI control.

the Arg16Gly and Gln27Glupolymorphisms. The analysis by MDR2.0 software, showed association with FEF25-75%; the response to Arg16Gly was respondent by 17.35% and Gln27Glu by 6.8% in variation found. Conclusion There was an association between the Arg16Gly and Gln27Glupolymorphisms in ADRB2 gene with CF´s severity and bronchodilator response.

Beta2-adrenergic receptor gene and neuropeptide Y gene may potentially influence lipid metabolism and overall energy balance. Therefore, we examined associations of these genes with lipid fractions and obesity-related phenotypes in hypertensive subjects. A total of 638 white individuals from 212 Polish families with clustering of essential hypertension were phenotyped for cardiovascular risk determinants. Each subject was genotyped for functional polymorphisms of beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of beta2-adrenergic receptor gene, Arg16Gln27 was overtransmitted to offspring with elevated levels of total cholesterol (Z=2.2; P=0.026) and LDL-cholesterol (Z=3.2; P=0.002). Individually, Leu7Pro was not associated with any of the metabolic phenotypes in family-based tests or case-control analyses. However, in the presence of Arg allele of Arg16Gly and Gln allele of Gln27Glu, homozygosity for Leu variant of the Leu7Pro polymorphism was associated with 2.1-increased odds ratio (confidence interval, 1.10 to 3.81; P=0.024) of elevated LDL in hypertensive subjects, independent of age, gender, body mass index, adjusted blood pressures, antihypertensive therapy, and use of nonselective beta-blockers and diuretics. Consistently, there was a significant multilocus association among variants of Arg16Gly, Gln27Glu, and Leu7Pro in hypertensive probands with elevated LDL (cases; P=0.028) but not in hypertensive subjects with normal LDL (controls). This study revealed an association of LDL-cholesterol with beta2-adrenergic receptor gene haplotype and provided evidence for epistatic interaction between beta2-adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.

目的 探讨β2肾上腺素受体基因(β2AR) Gln27Glu多态性对健康青年血脂及载脂蛋白比值的影响及在高糖低脂(HC/LF)膳食诱导的血脂及载脂蛋白比值变化中的作用.方法 56例健康志愿者,给予7d平衡膳食和6 d HC/LF膳食,于第1d、第8d及第14 d取12 h空腹静脉血,测定血脂和载脂蛋白(apo) AI、B100水平,计算甘油三酯/高密度脂蛋白胆固醇(TG/HDL-C)、log(TG/H DL-C)、总胆固醇(TC)/HDL-C、低密度脂蛋白胆同醇(LDL-C)/HDL-C、apoAI/apoB100值.提取基因组DNA,聚合酶链反应-限制性酶切法分析β2AR Gln27Glu位点多态性.结果 血脂及载脂蛋白比值的基础值及平衡膳食后,无论是受试人群整体还是将男女分组分析,CC基因型受试者与G等位基因携带者之间均无明显差异.HC/LF膳食后,在整体受试人群中,G等位基因携带者log(TG/HDL-C)高于CC基因型受试者(P=0.038);男女分组分析发现CC基因型受试者与G等位基因携带者之间血脂及载脂蛋白比值无明显差异.与HC/LF膳食前相比,在受试人群整体,HC/LF膳食后apoAI/apoB100在CC基因型受试者升高(P=0.021),LDL-C/HDL-C和TC/HDL-C在CC基因型和G等位基因携带者中均下降(P＜0.05).按性别分组后,男性受试者HC/LF膳食后LDL-C/HDL-C和TC/H DL-C在CC基因型及G等位基因携带者均降低(P＜0.05);女性CC基因型和G等位基因携带者HC/LF膳食后TG/HDL-C、log( TG/HDL-C)均升高(P＜0.05),TC/HDL-C均降低(P＜0.05),但LDL-C/HDL-C仅在CC基因型中降低(P=0.037).结论 β2AR基因Gln27Glu多态性G等位基因能够在健康青年女性抑制HC/LF膳食诱导的LDL-C/HDL-C降低.%Objective To investigate the effects of the Gln27Glupolymorphism of β2-adrenergic receptor (β2AR) on serum lipid and apolipoprotein ratios and its interaction with high-carbohydrate/low-fat (HC/LF) diet on the ratios in healthy youth. Methods After on a washout diet for seven days, fifty six healthy young subjects were given the

Objective To investigate the variation of β_2 adrenergic receptor (β_2AR) gene and its association with obesity in Chinese population. Methods The allele of β_2AR gene at Argl6Gly and Gln27Glu sites were analysed with polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in 396 people with Han nationality in Chengdu, among whom 126 had obesity. Results The allele frequencies of Arg and Gly at Argl6Gly site were 0. 571 and 0. 429 for the obese people, and 0. 559 and 0. 441 for the non-obese people, respectively. The allele frequencies of Gin and Glu at Gln27Glu site were 0. 920 and 0. 080 for the obese people, and 0. 916 and 0. 084 for the non-obese people, respectively. No significant differences were found in the genotype frequencies of the two sites between non-obese and obese people. The non-obese females and obese males with genotype Arg/Arg at Argl6Gly site had elevated serum TC and LDL-C levels compared with those who carried Arg/ Gly or Gly/Gly (P0.05).在Arg16Gly位点,非肥胖组女性和肥胖组男性Arg/Arg基因型携带者血清 TC 和 LDLC 水平分别高于Arg/Gly和Gly/Gly基因型携带者(P0.05).结论 β_2AR基因Arg16Gly和Gln27Glu多态性与成都地区中国汉族人肥胖无关联,但Arg16Gly位点对特定性别非肥胖及肥胖人群血清TC、LDLC及部分载脂蛋白水平有一定影响.

In asthma, beta(2)-adrenoceptor agonist responsiveness has been associated with Arg16Gly and Gln27Glupolymorphisms of the beta(2)-adrenoceptor. Since the guinea pig is extensively used as an animal model for asthma, we investigated the occurrence of possible polymorphism of the guinea pig beta(2)-a

Glu la ingesta de AGPI puede resultar en mayor pérdida de peso corporal.Objective: To evaluate the effect of diet and PPARγ2 and b2-adrenergic receptor genes on energy metabolism and body composition in obese women. Material and methods: 60 obese women, aged 34.59 ± 7.56 years were studied at the Department of Physiology and Nutrition at Navarra University. Anthropometric, biochemical,metabolic and molecular evaluations were carried out, and the women were submitted to short-term and longterm hypocaloric diets, varying the macronutrients. The groups were formed according to genepolymorphism, as follows: Pro12Pro(PPARγ2/Gln27Gln (ί2-adrenergic receptor genes - A, Pro12Pro (PPARγ2/Gln27Glu (b2- adrenergic receptor genes - B, Pro12Pro (PPARγ2/Glu27Glu (b2-adrenergic receptor genes-C and Pro1Ala (PPARγ2/Gln27Glu (b2-adrenergic receptor genes - D. Results: In group A, fat oxidation was correlated positively with body mass index (BMI, but an increase in fat and saturated fatty acids (SFA in the diet did not reflect in increased oxidation. In group B, total fat and SFA intake did not lead to fat oxidation increase. In group C, fat and complex carbohydrates (CHO resulted in lower fat oxidation, and long-term increase of monounsaturated fatty acid (MUFA intake resulted in increase of CHO oxidation and smaller weight loss. In group D, greater energy expenditure was obtained after diet high in SFA in a short-term, and fat basal and postprandial oxidation correlated positively with its intake. Hypocaloric diet high in polyunsaturated fatty acid (PUFA resulted inincrease of fat oxidation. Conclusions: Polymorphism in PPARγ2 gene resulted in increased fat oxidation, regardless of genotype of ί2- adrenergic receptor gene. It is recommended control of the total intake of fats and SFA in Pro12Pro/Gln27Gln and Pro12Pro/Gln27Glu, and complex CHO and MUFA in Pro12Pro/Glu27Glu. In Pro12Ala/Gln27Glu, AGPI intake can result in greater body weight loss.

Full Text Available Abstract Objective: To determine the influence of polymorphisms of the beta-2 adrenergic receptor (ADRB2 in triggering exercise-induced bronchospasm (EIB in adolescents. Methods: The subjects were divided into two groups: present EIB (EIB+ (n=45 and absent EIB (EIB− (n=115. The bronchial provocation test with exercise was performed with a protocol that consisted of walking/running for at least eight minutes at high intensity, i.e., >85% of maximum heart rate, considering EIB+ as a 10% decrease in forced expiratory volume in one second (FEV1. The genotyping of the ADRB2 gene was performed by the Taqman method, using the Step One Plus system. Independent t-test, Mann–Whitney and Chi-square tests, as well as Spearman's correlation coefficient were used for the statistical analysis. Results: Age, body weight, height, FEV1, FVC and FEV1/FVC ratio were lower in the EIB+ group when compared to EIB− (p<0.05. There were no significant differences in the proportion of the allele at position 27 and Arg16Gly and Gln27Glu genotypes between the EIB+ and EIB− groups (p=0.26; p=0.97 and p=0.43, respectively. However, there was a trend toward statistical significance regarding the greater proportion of the Gly16 allele for the EIB+ when compared to the EIB− group (p=0.08. Conclusions: The presence of polymorphisms associated with the Glu27 allele and Arg16Gly and Gln27Glu genotypes had no influence on EIB. However, the statistical trend toward greater frequency of the Gly16 allele in individuals with EIB+ can be considered evidence of the influence of polymorphisms of the ADBR2 gene on EIB in adolescents.

Full Text Available Objective: To investigate the association of Arg16Gly and Gln27Glupolymorphisms of β2-adrenergic receptor gene (ADRB2 with the occurrence of asthma and overweight and the gene's influence on anthropometric, clinic, biochemical and physical fitness variables in children and adolescents. Methods: Subjects were evaluated for allelic frequencies of the β2-adrenergic receptor gene, height, weight, body mass index (BMI, BMI Z-score, waist circumference (WC, pubertal stage, resting heart rate (HRres, blood pressure (BP, total cholesterol (TC, glucose, insulin, high density lipoprotein (HDL-C, low density lipoprotein (LDL-C, triglyceride (TG, Homeostasis Metabolic Assessment (HOMA2-IR, Quantitative Insulin Sensitivity Check Index (QUICKI and maximal oxygen uptake (VO2max. The participants were divided in four groups: overweight asthmatic (n=39, overweight non-asthmatic (n=115, normal weight asthmatic (n=12, and normal weight non-asthmatic (n=40. Results: Regarding the Gln27Glupolymorphism, higher total cholesterol was observed in usual genotype individuals than in genetic variant carriers (p=0.04. No evidence was found that the evaluated polymorphisms are influencing the physical fitness. The Arg16 allele was found more frequently among the normal weight asthmatic group when compared to the normal weight non-asthmatic group (p=0.02, and the Glu27 allele was more frequently found in the overweight asthmatics group when compared to the normal weight non-asthmatic group (p=0.03. Conclusions: The association of Arg16 allele with the occurrence of asthma and of the Glu27 allele with overweight asthmatic adolescents evidenced the contribution of the β2-adrenergic receptor gene to the development of obesity and asthma.

Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated w...

Since beta2-adrenergic receptors are important regulators of blood pressure, genetic variation in this receptor could explain risk of elevated blood pressure in selected individuals. We tested the hypothesis that Gly16Arg, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor gene associated...... with elevated blood pressure....

Functional and common Arg16Gly and Gln27Glupolymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results.......Functional and common Arg16Gly and Gln27Glupolymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results....

gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the 2- and 3-adrenergic receptors in humans. Further, 2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the -adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. 2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile have been studied in relation to hypertension. Genetic variations in the 3-adrenoceptor (i.e. Try64Arg variant are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of 2- and 3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and 2- and 3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.

Full Text Available Cardiovascular diseases (CVD include a heterogeneous group of multifactorial conditions and represent the major health problem in the western society. Many studies have evidenced that inter-individual variability affects the prognosis and the response to pharmacological treatment in patients with CVD. The identification of genetic markers to select patients more susceptible to develop cardiovascular complications has a therapeutic interest for undertaking individualized therapeutic approach. The sympathetic nervous system acts through adrenergic receptor subtypes and plays a key role in the development and prognosis of CVD. In particular, β-2 adrenergic receptors (β2AR, expressed in a wide variety of tissues, are critical regulators of cardiac output, peripheral vascular resistance and metabolism. Several variations with multiple single-nucleotide polymorphisms have been identified in β2AR gene. There are 3 common β2AR polymorphisms characterized in more detail for their influence on functional receptor activity. In particular, the changing an arginine for a glycine at position 16 of the receptor protein (Arg16Gly is associated with increased agonist-induced down-regulation; the substitution of glutamine with glutamic acid at position 27 (Gln27Glu leads to resistance to down-regulation; the substitution of threonine with isoleucine (Thr164Ile at position 164 causes receptor uncoupling from the G protein. Many studies have indicated the association of β2AR polymorphisms with various cardiovascular and metabolic diseases and have contributed to indicate the β2AR gene variants an appropriate target for investigating possible links between receptor polymorphisms, drug responses and susceptibility to CVD. However, the reports on the association of β2AR polymorphisms with clinical outcomes of CVD have been contradictory. In this review, we will illustrate the effects of β2ARs genetic variability on the management of CVD.

The prevalent rates of overweight and obesity are steadily increasing all over the world. Previous studies of some candidate genes have indicated that most of the genes are associated with obesity in human adipose tissue. As much as 40% of the variations in body mass could be attributed to genetic difference. The β-adrenergic receptor (β-AR) plays a major role in the regulation of energy balance in humans. A high sympathetic nervous system activity has been shown to be associated with obesity and is believed to have pathogenetic relevance. Several common single nucleotide polymorphisms (SNPs) including Gly389Arg in β1-AR, Gln27Glu in β2-AR, and Trp64Arg in β3-AR in humans could alter receptor function and these variations ofβ-ARs were shown to have certain association with obesity. Here we summarize the genetic polymorphisms of human β-ARs and their potential impacts to obesity.%在世界范围内,肥胖和超重的发生率正在稳步增长.过去有关候选基因的大量研究已经表明,大多数基因与人类脂肪组织中肥胖的发生相关.与人体体质量相关的40%以上的基因变异可以产生遗传差异.β-肾上腺素受体在人体能量平衡调节中扮演重要作用,交感神经系统的高度激活被认为与肥胖的发生密切相关.β-肾上腺素受体的单核苷酸多态性如β1-肾上腺素受体Gly389Arg,β2-肾上腺素受体Gln27Glu和β3-肾上腺素受体Trp64Arg已经被证明能够改变受体的功能,并与肥胖的发生有关.本文就β-肾上腺素受体的遗传多态性以及它们在肥胖发生中的作用作一综述.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Chronic heart failure (HF) is a syndrome with increasing prevalence. Though mortality is still high, the introduction of ß-adrenoceptor blockers for its treatment has improved survival considerably. • As is the case for all medical treatment, not all...... patients benefit from ß-adrenoceptor blocker treatment, and stratifying patients to different ß-adrenoceptor blockers by the use of pharmacogenomics might be of great value in improving HF therapy. • Previous studies have shown that the two single nucleotide polymorphisms (SNPs) ADRB1 Arg389Gly and ADRB2...... Gln27Glu interact with the ß-adrenoceptor blockers metoprolol and carvedilol, respectively. These interactions have led to stratified responses with regard to surrogate parameters, e.g. left ventricular ejection fraction (LVEF), pulse and blood pressure. • Several studies have failed to show...

Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se-quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mel itus (129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa-tients) and 268 healthy controls. Al subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistical y significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

Full Text Available We aimed to conduct a review of the literature for genepolymorphisms associated with chronic periodontitis (CP susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate genepolymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of genepolymorphisms in CP.

Full Text Available Abstract Background The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL cholesterol levels in these patients. The functionally relevant polymorphisms of the β2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. Methods We investigated a group of 429 patients (55 ± 10.7 years; 361 men, 68 women with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI 29.1 ± 23.1/h and, on average, a high cardiovascular risk profile (body mass index 31.1 ± 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients. We typed the β2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8% and survived myocardial infarction (n = 27, 6.3% were compared between the genotypes and haplotypes. Results Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The β2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR = 0.32, P = 0.012; Arg16Gly: n = 197, OR

In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin genepolymorphisms have drawn much attention in biomedical research. Leptin genepolymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically impo

In an era of rapidly increasing prevalence of human obesity and associated health problems, leptin genepolymorphisms have drawn much attention in biomedical research. Leptin genepolymorphisms have furthermore drawn much attention from animal scientists for their possible roles in economically

Full Text Available Leptin is a protein involved in the regulation of feed intake, fat metabolism, whole body energy balance, reproduction and hematopoiesis. In cattle Leptin gene has been considered a potential QTL influencing several production traits like meat production, milk performance and reproduction. Several studies on bovine leptin gene have found association between polymorphisms and traits like milk yield, feed intake, fat content, carcass and meat quality. With the aim to assess the presence of sequences polymorphisms in the Buffalo leptin gene, we sequenced the entire coding region and part of the introns on a panel of Italian River Buffalos. In this study we identified a new set of SNP (Single Nucleotide Polymorphism useful for association studies.

Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop several forms of cancer. Research carried out in the last decade demonstrated that several CYP enzymes are polymorphic due to single nucleotide polymorphisms, gene duplications and deletions. As genotyping procedures became available for most human CYP, an impressive number of association studies on CYP polymorphisms and cancer risk were conducted. Here we review the findings obtained in these studies regarding CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP8A1 and CYP21 genepolymorphisms. Consistent evidences for association between CYP polymorphisms and lung, head and neck, and liver cancer were reported. Controversial findings suggest that colorectal and prostate cancers may be associated to CYP polymorphisms, whereas no evidences for a relevant association with breast or bladder cancers were reported. We summarize the available information related to the association of CYP polymorphisms with leukaemia, lymphomas and diverse types of cancer that were investigated only for some CYP genes, including brain, esophagus, stomach, pancreas, pituitary, cervical epithelium, melanoma, ovarian, kidney, anal and vulvar cancers. This review discusses on causes of heterogeneity in the proposed associations, controversial findings on cancer risk, and identifies topics that require further investigation. In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided.

The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 genepolymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

Since oral squamous cell carcinoma (OSCC) is the most prevalent malignant cancer in the oral cavity, several researches have been performed to study the role of important enzymes in this disease. Among them, the matrix metalloproteinases (MMPs) are highlighted, due to the fact that they are proteinases responsible to degrade many extra-cellular matrix components, making possible the invasion of neoplasic cells. Important tools in cancer prognosis have been utilized aiming to correlate high levels of MMPs and OSCC, such as immunohistochemical, zymographic and mRNA detection methods. However, these techniques are usually applied after cancer detection, characterizing a curative but not a preventive medicine. Trying to make interventions before the development of the disease and making possible the identification of people at high risk and, analysis of modifications in MMP genes has been a chance for modern medicine. Recently, polymorphisms in MMP genes have been related to different neoplasias, including OSCC. Despite investigation is beginning, MMP genepolymorphisms seems to have a promising future in oral cancer research and some of the present results have shown that there are MMP polymorphisms related to an increased risk for developing oral cancer. Key words:Oral cancer, polymorphism, matrix metalloproteinase.

ABSTRACT: BACKGROUND: Genotype-phenotype association studies are typically based upon polymorphisms or haplotypes comprised of multiple polymorphisms within a single gene. It has been proposed that combinations of polymorphisms in distinct genes, which functionally impact the same phenotype, may hav

Conclusion: Polymorphisms of ADAM33 gene might be associated with severe asthma and sensitivity to aeroallergens in northeast of Iran, but further studies are needed to determine the polymorphisms in this area and other regions of our country.

Genome scans indicate a linkage of autism to the chromosome 7q21-q36 region. Recent studies suggest that the Reelin gene may be one of the loci contributing to the positive linkage between chromosome 7q and autism. However, these studies were relatively small scale, using a few markers in the gene. We investigated 34 single nucleotide polymorphisms (SNPs) in the Reelin gene with an average spacing between the SNPs of 15 kb for evidence of association with autism. There were significant differences in the transmission of the alleles of exon 22 and intron 59 SNP to autistic subjects. Our findings support a role for the Reelin gene in the susceptibility to autism.

Full Text Available Androgen receptor genes (AR have been found to have associations with reproductive development, behavioral traits, and disorders in humans. However, the influence of similar genetic effects on the behavior of other animals is scarce. We examined the loci AR glutamine repeat (ARQ in 44 Grevy's zebras, 23 plains zebras, and three mountain zebras, and compared them with those of domesticated horses. We observed polymorphism among zebra species and between zebra and horse. As androgens such as testosterone influence aggressiveness, AR polymorphism among equid species may be associated with differences in levels of aggression and tameness. Our findings indicate that it would be useful to conduct further studies focusing on the potential association between AR and personality traits, and to understand domestication of equid species.

Full Text Available The existence of selection on the rabbits with potential for meat has only been seen from phenotypic aspects including performance and productivity, while the molecular genetic studies are still very rare. One of the candidate genes for meat production traits in rabbit is myostatin. Totally 50 blood samples of male rabbits from Rex, Satin, Reza (crossing from Rex and Satin, Flemish Giant and FZ3 (crossing from Flemish Giant and Reza breed were used at Indonesian Research Institute for Animal Production (IRIAP. Genetic polymorphism by Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP method used FspBI restriction enzyme. PCR-RFLP data were analyzed by calculating allele and genotype frequencies. Sequencing was performed in rabbit with different genotypes which represents each of the samples. Genotype of AT had two cut points of the FspBI restriction enzyme at the base position of 508 bp and 444 bp. The cut point at the base position of 446 bp was site mutation base T became A. Genotype of TT had one cut point at the base position of 508 bp and no mutation site. Allele T had higher frequency than allele A and just Rex and Reza rabbit breeds had two alleles. The other rabbits (Satin, Flemish Giant and FZ3 only had one allele i.e., allele T. PCR - RFLP analysis of the MSTN|FspBI gene segments was polymorphic in Rex and Reza rabbit breeds. All of rabbit breeds in this study did not have AA genotype.

The distribution and frequency of single nucleotide polymorphisms (SNPs) can help to understand changes associated with characteristics of interest. We aimed to evaluate nucleotide diversity in six genes involved in starch biosynthesis in cassava using a panel of 96 unrelated accessions. The genes were sequenced, aligned, and used to obtain values for nucleotide diversity (π), segregating sites (θ), Tajima's D test, and neighbor-joining (NJ) clustering. On average, one SNP per 147 and 171 bp was identified in exon and intron regions, respectively. Thirteen heterozygous loci were found. Three of seven SNPs in the exon region resulted in non-synonymous replacement or four synonymous substitutions. However, no associations were noted between SNPs and root dry-matter content. The parameter π ranged from 0.0001 (granule bound starch synthase I) to 0.0033 (α-amylase), averaging 0.0011, while θ ranged from 0.00014 (starch branching enzyme) to 0.00584 (starch synthase I), averaging 0.002353. The θ diversity value was typically double that of the π. Results of the D test did not suggest any evidence of deviance of neutrality in these genes. Among the evaluated accession, 82/96 were clustered using the NJ method but without a clear separation of the root dry-matter content, root pulp coloration, and classification of the cyanogenic compound content. High variation in genes of the starch biosynthetic pathway can be used to identify associations with the functional properties of starch for the use of polymorphisms for selection purposes.

The genetic variability present in the APOE genepolymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool. To analyze the APOE genepolymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia. We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia. The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium. The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

AIM: To investigate whether the pro- and antiinflammatory cytokine genepolymorphisms, IL1B-511C/T,IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C,TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5'nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses,the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007).After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C;OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P =0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14,P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C;OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However,the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine genepolymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

Full Text Available Aim: Cerebrovascular diseases are complex multifactorial disorders showing an increased incidence with increasing age and affected by genetic and environmental factors. Although risk factors for cerebrovascular diseases include age, sex, lineage, hypertension, diabetes mellitus, hypercholesterolemia; in young cerebrovascular patients below age 45, genetic factors may also contribute to the etiology. In this retrospective study, prothrombotic genepolymorphisms which are thought to be related with formation of disease in young adults with cerebrovascular accident (CVA were investigated. Material and Method: In the current study, Methylenetetrahydropholate Reductase (MTHFR C677T and A129C; Prothrombin (Factor II G20210A; Factor V Leiden G1691A prothrombotic genepolymorphisms were evaluated for 43 young patients under the age of 45 with cerebrovascular accident history. Result: For 43 young patients with cerebrovascular incident history, the frequency of following polymorphisms were determined as follows; MTHFR C677T polymorphism heterozygous frequency is 46.1%, homozygous frequency is 9.3%; MTHFR A1298C polymorphism heterozygous frequency is 39.47%, homozygous frequency is 26.31%; Prothrombin polymorphism heterozygous and homozygous frequency is 2.3%; FactorV Leiden polymorphism heterozygous frequency is 9.3%. Discussion: After evaluation the experimental results, we believe that MTHFR gene C677T and A1298C polymorphisms might be risk factors in CVAs. It was observed that cigarette usage, hypertension and existence of family story in addition to these polymorphisms increase the available risk.

Jan 11, 2016 ... Obesity is caused by an imbalance between food intake and energy expenditure. The etiology of ... ried out under The Code of Ethics of the World Medical Asso- ..... polymorphisms in obese Mexican subjects. Am J Agric Biol ... Synergistic effect of LEP and LEPR genepolymorphism on body · mass index in ...

Full Text Available Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02 and MTOR (p = 0.02 and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04. All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.

The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

AIM: To examine the influence of lipoprotein lipase (LPL)genepolymorphism in ulcerative colitis (UC) patients.METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL genepolymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing.Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR= 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more numerous than those with H+/+ genotype (OR = 2.51, 95%CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P ＜ 0.01, OR = 6.46, 95% CI =1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for Pvu Ⅱ polymorphism (P＜ 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.CONCLUSION: Ser447stop and HindⅢ LPL polymorphisms may influence age of onset of UC, while HindⅢand PvuⅡ polymorphisms influence serum triglyceride in UC patients.

The association of genepolymorphism and susceptibility to hepatocellular carcinoma (HCC) has been widely studied in recent years. Gene mutations are closely related to HCC. Understanding and measuring the gene mutations are useful to reduce the incidence of HCC and improve its prognosis.

ALOX12 produces ligands for PPARγ thereby turning mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the ALOX12 gene on BMD and fracture risk in two Danish cohorts and found four polymorphisms and a haplotype thereof to be associated...... with BMD and fracture risk. INTRODUCTION: Stimulation of the PPARγ with ligands produced by the ALOX enzymes drives mesenchymal stem cells in an adipocyte direction at the expense of osteoblasts leading to decreased osteoblast number and BMD. Previously, polymorphisms in the ALOX12 gene have been...... and followed for up to 10 years. On the basis of linkage disequilibrium (LD) between SNPs throughout the gene and previous genetic association studies we chose ten polymorphisms for investigation. Genotyping was carried out using the Sequenom MassARRAY genotyping system and TaqMan assays. RESULTS: In AROS...

Full Text Available Background/Aims: Renalase is a recently discovered protein, which is likely involved in regulation of blood pressure in humans and animals. Previous studies suggest that renalase reflects kidney functioning. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp has been described. In this study we examined the association between (Glu37Asp polymorphism (rs2296545 in renalase gene and kidney allograft function. Methods: The study enrolled 270 Caucasian kidney allograft recipients. SNP within the renalase was genotyped using TaqMan genotyping assays. Results: There were no statistically significant associations between renalase gene rs2296545 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction as well as creatinine serum concentrations and blood pressure values after transplantation. Conclusions: The results of this study suggest, that renalase gene rs2296545 polymorphism is not important factor determining renal allograft function.

AIM: To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis. METHODS: Subjects included 170 unrelated adults (83 males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene. RESULTS: There was no significant difference in phenotype, allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls. CONCLUSION: This study demonstrates that MICA alleles studied bear no relation to cholelithiasis. PMID:12854159

AIM: To study the significance of polymorphism of MHC class I chain-related gene A (MICA) gene in patients with cholelithiasis.METHODS: Subjects included 170 unrelated adults (83males) with cholelithiasis and 245 randomly selected unrelated adults (130 males) as controls. DNA was extracted from peripheral leukocytes and analyzed for polymorphism of 5 alleles (A4, A5, A5.1, A6 and A9) of the MICA gene.RESULTS: There was no significant difference in phenotype,allele, and genotype frequencies of any of the 5 alleles between cholelithiasis patients and controls.CONCLUSION: This study demonstrates that MICA allelesstudied bear no relation to cholelithiasis.

Background: For the first time we tested an association between the human multidrug resistance gene 1 (MDR1) polymorphisms (SNPs) and idiopathic pulmonary fibrosis (IPF). Several MDR1 polymorphisms are associated with pathologies in which they modify the drug susceptibility and pharmacokinetics. Materials and Methods: We genotyped three MDR1 polymorphisms of 48 IPF patients and 100 control subjects with Italian origins. Results: No evidence of association was detected. Conclusion: There are 50 known MDR1 SNPs, and their role is explored in terms of the effectiveness of drug therapy. We consider our small-scale preliminary study as a starting point for further research. PMID:25767528

Full Text Available Aim. Autism is a subgroup of autism spectrum disorders, classified as a heterogeneous neurodevelopmental disorder and symptoms occur in the first three years of life. The etiology of autism is largely unknown, but it has been accepted that genetic and environmental factors may both be responsible for the disease. Recent studies have revealed that the genes involved in the folate/homocysteine pathway may be risk factors for autistic children. In particular, C677T polymorphism in the MTHFR gene as a possible risk factor for autism is still controversial. We aimed to investigate the possible effect of C677T polymorphism in a Turkish cohort. Methods. Autism patients were diagnosed by child psychiatrists according to DSM-IV and DSM-V criteria. A total of 98 children diagnosed as autistic and 70 age and sex-matched children who are nonautistic were tested for C677T polymorphism. This polymorphism was studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP methods. Results. MTHFR 677T-allele frequency was found to be higher in autistic children compared with nonautistic children (29% versus 24%, but it was not found statistically significant. Conclusions. We conclude that other MTHFR polymorphisms such as A1298C or other folate/homocysteine pathway genes may be studied to show their possible role in autism.

Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single genepolymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar....... The present Scandinavian results do not verify previous associations between the putative functional MTHFR genepolymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism...... disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences...

Autism is one of the most genetically influenced neuropsychiatric disorders. However, its detailed genetic basis is far from being clear. Genome-wide association studies have revealed a number of candidate genes, mostly related to synaptogenesis and various neuroendocrine pathways. In our study we have focused on oxytocin (OT), oxytocin receptor (OXTR), GABA receptor gamma 3 (GABRG3), neuroligin (NLGN4X), and reelin (RELN). After signed consent, 90 autistic boys and 85 healthy controls were enrolled in the study. Polymorphisms of OT (rs2740204), OXTR (rs2228485), GABRG3 (rs28431127), and NLGN4X (rs5916338) were analyzed using restriction fragment length polymorphism. (GGC)n STR polymorphism in the 5' UTR of the RELN gene was genotyped using fragment analysis. The only significant association in autistic boys in Slovakia was found with higher number of GGC repeats in the RELN gene (P=0.001) potentially explaining lower RELN levels in blood and brain of autistic patients.

disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences....... The present Scandinavian results do not verify previous associations between the putative functional MTHFR genepolymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism......Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single genepolymorphisms (SNPs; C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar...

Full Text Available THE mechanisms responsible for development of inflammatory bowel disease (IBD have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n=172 and healthy controls (n=389 for polymorphisms in genes encoding various cytokines (interleukin (IL-1β, IL-6, tumour necrosis factor (TNF, IL-10, IL-1 receptor antagonist. Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-α-308 polymorphism (p=0.0135. There was also variation in the frequency of IL-6-174 and TNF-α-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p=0.01. We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

We examined a panel of 21 patients diagnosed with compulsive buying for two DNA sequence polymorphisms found in the gene that encodes the serotonin transport (5-HTT). One polymorphism, found in the promoter region of the 5-HTT gene, involves a 44-base pair (bp) deletion, and the other, found in the second intron, is due to variable numbers of a repeat sequence. We also typed a panel of 38 psychiatrically normal controls for both 5-HH markers. When compared to this control panel, no significant differences were seen for either 5-HTT marker among the compulsive buyers.

Full Text Available The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR genepolymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR genepolymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection. PMID:28280748

Full Text Available Keratoconus (KC is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER. Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.–1370T>A polymorphism of the DNA polymerase γ (POLG gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1 were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1 nor the c.2285T>C polymorphism of the poly(ADP-ribose polymerase-1 (PARP-1 was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease.

Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 genepolymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect.

Full Text Available Background and Aims: In view of the prevailing controversy about the role of Methylenetetrahydrofolate reductase (MTHFR C677T mutation in stroke and paucity of studies from India, this study has been undertaken to evaluate MTHFR C677T genepolymorphism in consecutive ischemic stroke patients and correlate these with folic acid, homocysteine (Hcy and conventional risk factors. Settings and Design: Ischemic stroke patients prospectively evaluated in a tertiary care teaching hospital. Materials and Methods: Computerized tomography proven ischemic stroke patients were prospectively evaluated including clinical, family history of stroke, dietary habits and addictions. Their fasting and postprandial blood sugar, lipid profile, vitamin B12, folic acid and MTHFR gene analysis were done. Statistical Analysis: MTHFR genepolymorphism was correlated with serum folic acid, Vitamin B12 and Hcy levels; family history of stroke in first-degree relatives; and dietary habits; employing Chi-square test. Results: There were 58 patients with ischemic stroke, whose mean age was 50 (4-79 years; among them, 10 were females. MTHFR genepolymorphism was present in 19 (32.8% patients, 3 were homozygous and 16 were heterozygous. Both serum folate and B12 levels were low in 29 (50% patients and Hcy in 48 (83%. Hypertension was present in 28 (48% patients, diabetes in 12 (21%, hyperlipidemia in 52 (90%, smoking in 17 (29%, obesity in 1 (1.7% and family history of stroke in first-degree relatives in 13 (22.4%. There was no significant relationship of MTHFR genepolymorphism with folic acid, B12, Hcy levels, dietary habits and number of risk factors. Vitamin B12 level was low in vegetarians ( P Conclusion: MTHFR genepolymorphism was found in one-third of patients with ischemic stroke and was insignificantly associated with higher frequency of elevated Hcy.

Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana

Full Text Available Introduction & Objective: Periodontitis is a multifactorial disease in which host immune system and genetic factors have an important role in its pathogenesis. Genetic polymorphisms in cytokines and their receptors have been proposed as potential markers for periodontal diseases. The aim of the present study was to evaluate whether IL-4R genepolymorphism is associated with chronic periodontitis (CP or not? Materials & Methods: In this cross sectional study ninety non smoker patients (61 women and 29 men with chronic periodontitis were selected according to established criteria. They were categorized into three groups according to their clinical attachment level (CAL. Mutation at position 375(alanine/glutamine, 411(leucine/serine, 478(serine/proline, 406 (arginine/ cysteine in the IL-4R gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP method.Results: The distribution of mutations for IL-4 polymorphism at amino acids 375 (P=0.41, 411(P=0.22, 478(P=0.17, 406(P=0.77 were not significantly different among mild, moderate and sever chronic periodontitis patients. Conclusion: This study suggests that there is no correlation between IL-4R polymorphism of chronic periodontitis.(Sci J Hamadan Univ Med Sci 2011;18(3:63-69

Full Text Available Matrix metalloproteinases (MMPs play an important role in the pathogenesis of atherosclerosis, the pathology underlying the majority of coronary artery disease (CAD. In this study we tested the hypothesis that polymorphic variation in the MMP genes influences the risk of developing atherosclerosis. We analyzed functional polymorphisms in the promoter of the MMP-1, MMP-3, MMP-9 and MMP-12 genes in 183 Brazilian Caucasian individuals submitted to coronary angiography, of which 67 (37% had normal coronary arteries (control group and 116 (63% had CAD (CAD patient group. The -1607 1G/2G MMP-1, -1171 5A/6A MMP-3, -1562 C/T MMP-9, -82 A/G MMP-12 polymorphisms were analyzed by PCR followed by restriction digestion. No significant differences were observed in allele frequencies between the CAD patients and controls. Haplotype analysis showed no differences between the CAD patients and controls. There was a significant difference in the severity of CAD, as assessed by the number of diseased vessels, in MMP-1 1G/1G homozygous individuals and in those homozygous for the 6A allele of the MMP-3 polymorphism. However, multivariate analysis showed that diabetes mellitus was the only variable independently associated with CAD severity. Our findings indicated that MMP polymorphisms have no significant impact on the risk and severity of CAD.

textabstractCONTEXT: Interindividual variation in glucocorticoid (GC)-sensitivity can be partly explained by polymorphisms in the GC receptor (GR) gene. The ER22/23EK and N363S polymorphisms have been described to be associated with lower and higher GC sensitivity, respectively. OBJECTIVE AND DESIGN

Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

The human SNAIL is an important developmental protein involved in the formation of mesoderm and neural crest. The protein contains three classic and one atypical zinc-finger motif. The SNAI1 gene is composed of three exons. We have identified three SNPs in non-coding regions, two in the 5'UTR and one in intron 1, which can be detected by PCR followed by restriction enzyme digestion. We also identified a GGG/GGGG polymorphism in intron 1. We screened CEPH DNAs for these polymorphisms. Copyright 2001 Academic Press.

Objective. We assessed whether polymorphisms of GST genes (GSTM1, GSTT1, and GSTP1 are associated with asthma and atopy among Tunisian children. Methods. 112 unrelated healthy individuals and 105 asthmatic (73 atopic and 32 nonatopic children were studied. Genotyping the polymorphisms in the GSTT1 and GSTM1 genes was performed using the multiplex PCR. The GSTP1 ILe105Val polymorphism was determined using PCR-RFLP. Results. GSTM1 null genotype was significantly associated with the increased risk of asthma (P=.002. Asthmatic children had a higher prevalence of the GSTP1Ile105 allele than the control group (43.8% and 33.5%, respectively; P=.002. Also, the presence of the GSTP1 homozygote Val/Val was less common in subjects with asthma than in control group. We have found that GSTT1 null genotype (GSTT10∗/0∗ was significantly associated with atopy (P=.008. Conclusion. Polymorphisms within genes of the GST superfamily were associated with risk of asthma and atopy in Tunisia.

Background: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter genepolymorphism in patients with RAS and compare it with normal individuals. Materials and Methods: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. Results: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Conclusion: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene. PMID:27274339

populations have only revealed a limited polymorphism. We investigated the polymorphism of the exon 3 of HLA-G by means of Polymerase Chain Reaction (PCR)-Single Strand Conformation Polymorphism (SSCP)- and DNA sequencing analysis in a Danish population. We detected four single-base substitutions in exon 3...... rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...... compared to the sequence of HLA-6.0 (G*01011); one of these has not been reported before. We also found a deletion of the first base of codon 130 or the third of codon 129 in a heterozygous individual. This study, together with previous results, suggests that the polymorphism of exon 3 of the HLA-G gene...

Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT...

Full Text Available Background/Aim. Atherosclerosis is still the leading cause of death in Western world. Development of atherosclerotic plaque involves accumulation of inflammatory cells, lipids, smooth muscle cells and extracellular matrix proteins in the intima of the vascular wall. Apolipoprotein E participates in the transport of exogenous cholesterol, endogenouly synthesized lipids and triglycerides in the organism. Apolipoprotein E gene has been identified as one of the candidate genes for atherosclerosis. Previous studies in different populations have clearly implicated apolipoprotein E genetic variation (ε polymorphisms as a major modulator of low density lipoprotein cholesterol levels. Data considering apolipoprotein E polymorphisms in relation to carotid atherosclerosis gave results that are not in full compliance. The aim of present study was to investigate the apolipoprotein E polymorphisms in association with carotid plaque presence, apolipoprotein E and lipid serum levels in patients with carotid atherosclerosis from Serbia. Methods. The study group enrolled 495 participants: 285 controls and 210 consecutive patients with carotid atherosclerosis who underwent carotid endarterectomy. Genotyping of apolipoprotein E polymorphisms were done using polymerase chain reaction and restriction fragment length polymorphism methods. Results. Patients had significantly decreased frequency of the ε2 allele compared to controls. Patients who carry at least one ε2 allele had a significantly higher level of serum apolipoprotein E and significantly lower low density lipoprotein cholesterol levels compared to those who do not carry this allele. Conclusion. Our results suggest protective effect of apolipoprotein E ε2 allele on susceptibility for carotid plaque presence as well as low density lipoprotein cholesterol lowering effect in Serbian patients with carotid atherosclerosis. Further research of multiple gene and environmental factors that contribute to the

Knowledge of candidate genepolymorphisms in a population is useful for a variety of gene-disease association studies, particularly for some complex traits. A single nucleotide variant of the angiotensinogene gene (AGT M235T) and endothelial nitric oxide synthase gene (eNOS G894T) have been associated with hypertension. A cross-sectional study consisting of 200 hypertensives and 198 age- and sex-matched controls was conducted. Subjects involved in this study were pure Malay for 3 generations. The AGT M235T and eNOS G894T polymorphisms were determined by PCR-RFLP method. The distribution of M235T genotype in the population was 3.5% for MM, 30.4% for MT and 66.1% for TT. No significant difference was observed in genotype (chi(2)=1.30, p=0.52) and allele (chi(2)=0.87, p=0.35) frequencies among the 2 study group. In contrast, the distribution of genotypes for G894T was 74.1% for GG, 24.6% for GT and 1.3% for TT, respectively. Similarly, no significant difference was observed in genotype (chi(2)=0.94, p=0.33) and allele (chi(2)=0.60, p=0.44) frequencies between both study groups. The AGT M235T and eNOS G894T polymorphisms are unlikely to play an important role in the pathogenesis of hypertension in Malays.

We developed a new method based on the single strand conformation polymorphism (SSCP) technique for the detection of a G23591A (Asp312Asn) polymorphism in exon 10 of the XPD gene. In the process we also identified a novel polymorphism 23623C-ins (IVS10+17C-ins) in intron 10 of the same gene. With this newly developed SSCP-based method of genotyping we could detect both polymorphisms in the same assay and thus consequently determine the haplotype. In order to determine the population frequency of the novel polymorphism and the haplotype frequency, 302 healthy individuals were genotyped. The allelic frequency of the 23623C-ins intronic polymorphism was 0.16, whereas the frequency of the variant allele for the G23591A polymorphism was 0.39. Forty-three individuals (14%) were heterozygous for both polymorphisms but none carried polymorphic variants for both G23591A and 23623C-ins on the same allele. The effect of the novel intronic insertion polymorphism, which is located 16 nt downstream of the 3'-end of exon 10 of the XPD gene and involves a mononucleotide C repeat sequence, on expression remains to be determined.

Full Text Available Stroke is a common disease which has serious impact on human health in modern society. It has complex pathogenesis and wide-ranging influencing factors. Accompanied with the development of molecular genetics, a number of single nucleotide polymorphisms (SNPs have been found to be closely related to the incidence of stroke in case-control studies on the correlation between genes and stroke by using molecular biology technologies. In order to have a better understanding on the correlation between genepolymorphism and stroke, this summary presents a review of literatures reported at home and abroad over the past year on the genetics of stroke. DOI: 10.3969/j.issn.1672-6731.2015.02.002

Full Text Available Abstract Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs. Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD.

Full Text Available Genepolymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R genepolymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject’s arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Full Text Available Genepolymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R genepolymorphism (rs879576 with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant. There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239. Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239. The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

In a sample of 569 Chinese high school students, the present findings indicated that students with the 4-repeat genotype showed a higher level of test anxiety. Furthermore, the prediction of academic performance on test anxiety was stronger among students with the 3-repeat genotype than those with the 4-repeat genotype. The present findings suggest that mono-amine-oxidase type A genepolymorphism is significantly related to test anxiety.

Genepolymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R genepolymorphism (rs879576) with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP) technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant). There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239). Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239). The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.

Full Text Available Yanbo Lv, Shuangyan Lin, Fang Peng Department of Pathology, Zhejiang Hospital, Hangzhou City, Zhejiang, China Objective: Lung cancer, which is the leading cause of cancer death worldwide, is influenced by a wide variety of environmental and genetic risk factors. The silent information regulator 1 (SIRT1 gene is located on the long arm of chromosome 10 (10q21.3 and has been shown to play crucial roles in lung cancer development in previous studies. In this study, we determined whether variation in the SIRT1 gene is associated with lung cancer in Chinese population.Methods: The case–control study comprised 246 controls and 257 non-small cell lung cancer patients, comprising 79 squamous cell carcinoma patients and 124 adenocarcinoma patients. All subjects were from Zhejiang, China. Four single-nucleotide polymorphisms of SIRT1 gene were analyzed: rs12778366 (C/T, lies in the 5′ upstream, rs3758391 (C/T, lies in the 5′ upstream, rs2273773 (C/T, lies in the coding and rs4746720 (C/T, lies in the 3′ untranslated region.Results: No significant difference of allele and genotype frequencies was observed between the different groups. Haplotype association analysis carried out on the four single-nucleotide polymorphisms within the case–control cohort also did not reveal a significant association with lung cancer (P>0.05.Conclusion: The results suggest the tested SIRT1 genepolymorphisms may not contribute to lung cancer. Further studies are warranted to demonstrate the functional roles of the SIRT1 polymorphism in lung cancer. Keywords: SIRT1, SNP, non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma

Full Text Available Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past.

Full Text Available Periodontal diseases are inflammatory diseases of supporting structures of the tooth. It results in the destruction of the supporting structures and most of the destructive processes involved are host derived. The processes leading to destruction and regeneration of the destroyed tissues are of great interest to both researchers and clinicians. The selective susceptibility of subjects for periodontitis has remained an enigma and wide varieties of risk factors have been implicated for the manifestation and progression of periodontitis. Genetic factors have been a new addition to the list of risk factors for periodontal diseases. With the availability of human genome sequence and the knowledge of the complement of the genes, it should be possible to identify the metabolic pathways involved in periodontal destruction and regeneration. Most forms of periodontitis represent a life-long account of interactions between the genome, behaviour, and environment. The current practical utility of genetic knowledge in periodontitis is limited. The information contained within the human genome can potentially lead to a better understanding of the control mechanisms modulating the production of inflammatory mediators as well as provides potential therapeutic targets for periodontal disease. Allelic variants at multiple gene loci probably influence periodontitis susceptibility.

Full Text Available Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L (P<0.05. Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism.

Calpains are calcium-regulated protcases involved in cellular functions that include muscle proteolysis both ante- and postmortem. This study was designed to clone the complete coding sequence of the porcine calpain10 gene, CAPN10, to analyze its expression characteristics and to investigate its polymorphism. Two isoforms of the CAPN10 gene, CAPN10A and CAPN10B, were obtained by reverse transcriptionpolymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends methods combined with in silico cloning. RT-PCR results indicated that CAPN10 mRNA was ubiquitously expressed in all tissues examined and, with increasing age,the expression level increased in muscles at six different growth points. In the same tissues, the expression level of CAPN10A was higher than that of CAPN10B. In addition,three single nucleotide polymorphisms were detected by the PCR-single-stranded conformational polymorphism method and by comparing the sequences of Chinese Min pigs with those of Yorkshire pigs. C527T mutation was a missense mutation and led to transforming Pro into Leu at the 176th amino acid. The results of the current study provided basic molecular information for further study of the function of the porcine CAPN10 gene.

Full Text Available Objective. To assess frequency distribution of estrogenic receptor (ERa and ERfl genepolymorphisms and their influence on bone mineral density (BMD in groups of postmenopausal women with and without osteoporosis (OP. Material and methods. 200 residents of Moscow and Moscow region were divided into two groups considering BMD values according to WHO criteria; OP group and healthy control group Results. Differences of genotype and their combinations frequency distribution between OP and control groups show presence OP risk and protector genotypes. ER gene important role in pathogenesis of postmenopausal osteoporosis and possibility to use these genetic markers for assessment of risk of OP development in Russian population was confirmed.

The interleukin 18 receptor (IL18R1) gene is a strong candidate gene for asthma. It has been implicated in the pathophysiology of asthma and maps to an asthma susceptibility locus on chromosome 2q12. The possibility of association between polymorphisms in IL18R1 and asthma was examined...... by genotyping seven SNPs in 294, 342 and 100 families from Denmark, United Kingdom and Norway and conducting family-based association analyses for asthma, atopic asthma and bronchial hyper-reactivity (BHR) phenotypes. Three SNPs in IL18R1 were associated with asthma (0.01131 ... in IL18R1 and asthma....

Full Text Available Abstract Background Chronic rhinosinusitis (CRS is increasingly viewed as an inflammatory condition of the sinonasal mucosa interacting with bacteria and/or fungi. However, factors conferring susceptibility to disease remain unknown. Advances in genomics offer powerful tools to explore this disorder. The goal of this study was to evaluate the effect of single nucleotide polymorphisms (SNP on CRS in a panel of genes related to cysteinyl leukotriene metabolism. Methods Severe cases of CRS and postal code match controls were recruited prospectively. A total of 206 cases and 200 controls were available for the present study. Using a candidate gene approach, five genes related to cysteinyl leukotriene metabolism were assessed. For each gene, we selected the maximally informative set of common SNPs (tagSNPs using the European-derived (CEU HapMap dataset. These SNPs are in arachidonate 5-lipoxygenase (ALOX5, arachidonate 5-lipoxygenase-activating protein (ALOX5AP, leukotriene C4 synthase (LTC4S, cysteinyl leukotriene receptor 1 (CYSLTR1 and cysteinyl leukotriene receptor 2 (CYSLTR2 genes. Results A total of 59 SNPs were genotyped to capture the common genetic variations within these genes. Three SNPs located within the ALOX5, CYSLTR1 and ALOX5AP genes reached the nominal p-value threshold (p Conclusion While these initial results do not support that polymorphsims in genes assessed involved in the leukotriene pathways are contributing to the pathogenesis of CRS, this initial study was not powered to detect polymorphisms with relative risk of 2.0 or less, where we could expect many gene effects for complex diseases to occur. Thus, despite this lack of significant association noted in this study, we believe that validation with external populations and the use of better-powered studies in the future may allow more conclusive findings.

Full Text Available Sequence polymorphisms among and within four Acacia species, A. aulacocarpa, A. auriculiformis, A. crassicarpa, and A. mangium, were investigated using four chloroplast DNA genes (atpA, petA, rbcL, and rpoA. The phylogenetic relationship among these species is discussed in light of the results of the sequence information. No intraspecific sequence variation was found in the four genes of the four species, and a conservative rate of mutation of the chloroplast DNA genes was also confirmed in the Acacia species. In the atpA and petA of the four genes, all four species possessed identical sequences, and no sequence variation was found among the four Acacia species. In the rbcL and rpoA genes, however, sequence polymorphisms were revealed among these species. Acacia aulacocarpa and A. crassicarpa shared an identical sequence, and A. auriculiformis and A. mangium also showed no sequence variation. The fact that A. mangium and A. auriculiformis shared identical sequences as did A. aulacocarpa and A. crassicarpa indicated that the two respective species were extremely closely related. Although a putative natural hybrid of A. aulacocarpa and A. auriculiformis has been reported, our results suggested that natural hybridization should be further verified using molecular markers.

The complementary sex determination (csd) gene is the primary gene determining the gender of honey bees (Apis spp). In this study we analyzed the polymorphism of csd gene in six Apis mellifera subspecies. The genomic region 3 of csd gene in these six A. mellifera was cloned, and identified. A total of 79 haplotypes were obtained from these six subspecies. Analysis showed that region 3 of csd gene has a high level of polymorphism in all the six A. mellifera subspecies. The A. m. anatolica subspecies has a slightly higher nucleotide diversity (π) than other subspecies, while the π values showed no significant difference among the other five subspecies. The phylogenetic tree showed that all the csd haplotypes from different A. mellifera subspecies are scattered throughout the tree, without forming six different clades. Population differentiation analysis showed that there are significant genetic differentiations among some of the subspecies. The NJ phylogenetic tree showed that the A. m. caucasica and A. m. carnica have the closest relationship, followed by A. m. ssp, A. m. ligustica, A. m. carpatica and A. m. anatolica that were gathered in the tree in turn.

Full Text Available Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and occasionally in humans. Prevention of the disease has been mainly by monthly use of the macrocyclic lactone (ML endectocides during the mosquito transmission season. Recently, ML resistance has been confirmed in D. immitis and therefore, there is a need to find new classes of anthelmintics. One of the mechanisms associated with ML resistance in nematodes has been the possible role of ATP binding cassette (ABC transporters in reducing drug concentrations at receptor sites. ABC transporters, mainly from sub-families B, C and G, may contribute to multidrug resistance (MDR by active efflux of drugs out of the cell. Gene products of ABC transporters may thus serve as the targets for agents that may modulate susceptibility to drugs, by inhibiting drug transport. ABC transporters are believed to be involved in a variety of physiological functions critical to the parasite, such as sterol transport, and therefore may also serve as the target for drugs that can act as anthelmintics on their own. Knowledge of polymorphism in these ABC transporter genes in nematode parasites could provide useful information for the process of drug design. We have identified 15 ABC transporter genes from sub-families A, B, C and G, in D. immitis, by comparative genomic approaches and analyzed them for polymorphism. Whole genome sequencing data from four ML susceptible (SUS and four loss of efficacy (LOE pooled populations were used for single nucleotide polymorphism (SNP genotyping. Out of 231 SNPs identified in those 15 ABC transporter genes, 89 and 75 of them were specific to the SUS or LOE populations, respectively. A few of the SNPs identified may affect gene expression, protein function, substrate specificity or resistance development and may be useful for transporter inhibitor/anthelmintic drug design, or in order to anticipate resistance development.

Full Text Available Abstract Background Hemoglobin (Hb polymorphism, assessed by protein gel electrophoresis, has been used almost exclusively to characterize the genetic structure of Atlantic cod (Gadus morhua populations and to establish correlations with phenotypic traits such as Hb oxygen binding capacity, temperature tolerance and growth characteristics. The genetic system used to explain the results of gel electrophoresis entails the presence of one polymorphic locus with two major alleles (HbI-1; HbI-2. However, vertebrates have more than one gene encoding Hbs and recent studies have reported that more than one Hb gene is present in Atlantic cod. These observations prompted us to re-evaluate the number of Hb genes expressed in Atlantic cod, and to perform an in depth search for polymorphisms that might produce relevant phenotypes for breeding programs. Results Analysis of Expressed Sequence Tags (ESTs led to the identification of nine distinct Hb transcripts; four corresponding to the α Hb gene family and five to the β Hb gene family. To gain insights about the Hb genes encoding these transcripts, genomic sequence data was generated from heterozygous (HbI-1/2 parents and fifteen progeny; five of each HbI type, i.e., HbI-1/1, HbI-1/2 and HbI-2/2. β Hb genes displayed more polymorphism than α Hb genes. Two major allele types (β1A and β1B that differ by two linked non-synonymous substitutions (Met55Val and Lys62Ala were found in the β1 Hb gene, and the distribution of these β1A and β1B alleles among individuals was congruent with that of the HbI-1 and HbI-2 alleles determined by protein gel electrophoresis. RT-PCR and Q-PCR analysis of the nine Hb genes indicates that all genes are expressed in adult fish, but their level of expression varies greatly; higher expression of almost all Hb genes was found in individuals displaying the HbI-2/2 electrophoretic type. Conclusion This study indicates that more Hb genes are present and expressed in adult

Grain protein content (GPC) is a key quality factor for malting and brewing process. In wheat, a QTL explaining a large part of GPC variation was identified, which co-localizes with a gene encoding a NAC transcription factor (TtNAM-B1). NAC transcription factors influence GPC by their role in the regulation of senescence and in protein remobilization. An orthologous gene was discovered on barley chromosome 6H where a GPC QTL was mapped. In this study, we identify allelic variation of the NAM-1 gene for three species of Hordeum representing wild and cultivated barley and we investigate the possible link with GPC. Three haplotypes were identified, one corresponds to the sequences of 11 European varieties representing H. vulgare, one corresponds to the sequence found in H. spontaneum and one represents the sequence of H. bulbosum. Three SNPs were identified between H. spontaneum sequence and H. vulgare sequence. One of the H. bulbosum polymorphisms leads to the introduction of a stop codon and a non-functional protein. Differences in GPC between the 11 varieties were found but no polymorphism in the NAM-1 gene was observed, suggesting that differences in expression of the HvNAM-1 gene or other genes should play a role in GPC regulation. Nevertheless based on published values for GPC of H. bulbosum and H. spontaneum compared to GPC measured here in H. vulgare, the non-functional protein is associated with the lower GPC, suggesting that loss of functionality of the NAM-1 gene in Hordeum is related to lower GPC. Moreover H. spontaneum GPC seems to be higher than H. vulgare GPC, suggesting also that allelic variation of the functional NAM-1 gene could be associated with GPC variation within the genus Hordeum. Copyright 2009 Elsevier GmbH. All rights reserved.

Gene-for-gene relationships are a common feature of plant-parasite interactions. Polymorphism at host resistance and parasite avirulence loci is maintained if there is negative, direct frequency-dependent selection on alleles of either gene. More specifically, selection of this kind is generated when the disease is polycyclic with frequent auto-infection. When an incompatible interaction occurs between a resistant host and an avirulent parasite, systemic defenses are triggered, rendering the plant more resistant to a later attack by another parasite. However, induced resistance (IR) incurs a fitness cost to the plant. Here, the effect of IR on polymorphism in gene-for-gene interactions is investigated. First, in an infinite population model in which parasites have two generations per host generation, increasing the fitness cost of IR increases selection for susceptible plants at low disease severity, while increasing the effectiveness of IR against further parasite attacks enhances selection for resistant plants at high disease severity. This reduces the possibility of polymorphism being maintained in host and parasite populations. In finite population models, the number of plants varies over time as a function of the disease burden of the population. Polymorphism in gene-for-gene relationships is then more stable at high disease prevalence and severity if IR reactions are more costly when there is competition for resources between plants.

Brazil is the world's largest producer of beef cattle; however, the quality of its herds needs to be improved. The use of molecular markers as auxiliary tools in selecting animals for reproduction with high pattern for beef production would significantly improve the quality of the final beef product in Brazil. The leptin gene has been demonstrated to be an excellent candidate gene for bovine breeding. The objective of this study was to sequence and compare the leptin gene promoter of Brazil's important cattle breeds in order to identify polymorphisms in it. Blood samples of the Nellore, Guzerat, Tabapuã, and Senepol breeds were collected for genomic DNA extraction. The genomic DNA was used as a template for polymerase chain reaction (PCR) to amplify a 1575-bp fragment, which in turn was sequenced, aligned, and compared between animals of different breeds. Twenty-three single nucleotide polymorphic sites, including transitions and transversions, were detected at positions -1457, -1452, -1446, -1397, -1392, -1361, -1238, -963,-901, -578, -516, -483, -478, -470, -432, -430, -292, -282, -272, -211, -202, -170, and -147. Additionally, two insertion sites at positions -680 and -416 and two deletion sites at positions -1255 and -1059 were detected. As the promoter region of the leptin gene has been demonstrated to vary among breeds, these variations must be tested for their use as potential molecular markers for artificial selection of animals for enhanced beef production in different systems of bovine production in Brazil.

Full Text Available Abstract Background The pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (FTO; however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion. Methods We searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR and their 95% confidence intervals (CI were estimated using per-allele comparison. Summary ORs were estimated using a random effects model. Results We identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36, rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53, rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38, rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68, and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62. Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with I2 test values ranging from 38.1% to 84.5%. Conclusions This meta-analysis suggests that FTO may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.

Hindiii and S447x polymorphisms of lipoprotein lipase gene and their relationship to coronary artery disease. ... Lipoprotein lipase is a key enzyme in lipoprotein metabolism and its gene is a major candidate gene for coronary ... Article Metrics.

textabstractThe prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the prion protein production as well as polymorphisms in

An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is a useful predictor of human plasma ACE levels. ACE levels tend to be lowest in subjects with ACE genotype DD and intermediate in subjects with ACE genotype ID. Angiotensin II (Ang II) as a product of ACE is a cardiac growth factor and produces a marked hypertrophy of the chick myocyte in cell culture. Rat experiments also suggest that a small dose of ACE inhibitor that does not affect the afterload results in prevention or regression of cardiac hypertrophy. In order to study the relationship of ACE and the severity of hypertrophy, the ACE genotype has been determined in 28 patients with a clinical diagnosis of familial hypertrophic cardiomyopathy (FHC) and 51 normal subjects. The respective frequencies of I and D alleles were: 0.52 and 0.48 (in FHC patients) and 0.44 and 0.56 (in the normal controls). There was no significant difference in the allele frequencies between FHC and normal subjects ({chi}{sup 2}=0.023, p>0.05). The II, ID, and DD genotypes were present in 7, 15, and 6 FHC patients, respectively. The averages of maximal thickness of the interventricular septum measured by echocardiography or at autopsy were 18 {plus_minus}3, 19{plus_minus}4, and 19{plus_minus}3 mm in II, ID and DD genotypes, respectively. The ACE genepolymorphism did not correlate with the severity of left ventricular hypertrophy in FHC patients (r{sub s}=0.231, p>0.05). These results do not necessarily exclude the possible effect of Ang II on the hypertrophy since the latter may be produced through the action of chymase in the human ventricles. However, ACE genepolymorphism is not a useful predictor of the severity of myocardial hypertrophy in FHC patients.

Full Text Available The aim of the study was to evaluate the association between swimming performance and the -9/+9 (rs5810761 polymorphism within the BDKRB2 gene in successful competitive swimmers.Best individual swimming results expressed in FINA points achieved at short, middle and long distance events of 157 well-trained Polish swimmers were incorporated into an analysis. Athletes’ genotype and allele distributions were analysed in comparison to 230 unrelated sedentary subjects who served as controls with the χ2 test. All samples were genotyped for the BDKRB2 -9/+9 polymorphism using the polymerase chain reaction (PCR. The effects of genotype on swimming performance were analysed with two-way (3 x 2; genotype x gender analysis of variance with metrical age as a covariate for each distance specialization. No statistical differences in the genotype and allele frequencies were found in long distance swimmers when compared with the total group of swimmers or controls. The BDKRB2 +9/-9 genotype had no significant effect on swimming performance at short, middle or long distance, regardless of gender. The results of this study do not support the hypothesis that the BDKRB2 -9/+9 polymorphism is associated with swimming performance in Polish swimmers.

Background Presence of xenotropic murine leukemia virus–related virus and chronic inflammation in prostate tumor suggests that inflammation plays a role in prostate cancer etiology. This study investigated whether variants in inflammatory genes act alone or interact with plasma antioxidants to influence prostate cancer risk in a population-based case-control study in Central Arkansas. Methods Cases (n = 193) were men, aged 40–80, diagnosed with prostate cancer in three major hospitals in 1998–2003, and controls (n = 197) were matched to cases by age, race, and county of residence. Results After adjustment for confounders, polymorphisms in COX-2 (rs689466) and IL-8 (rs4073) were not significantly associated with prostate cancer risk. However, apparent interactions were observed between these genetic variants and plasma antioxidants on the risk of this malignancy. The protective effect of the mutant allele of the COX-2 polymorphism was more pronounced among subjects with high plasma levels of β-cryptoxanthin, lycopene, β-carotene, or selenium (≥median) [e.g., OR (95% CI): 0.37 (0.15, 0.86) (AG/GG vs. AA) for β-cryptoxanthin]. Conversely, the promoting effect of the variant allele of the IL-8 polymorphism was more remarkable in subjects with low plasma levels of Lutein/zeaxanthin, β-cryptoxanthin, and β-carotene (antioxidants to modulate prostate cancer risk. PMID:20431935

The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphicgene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D(1), D(2), and D(4) receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D(3) and D(5) receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.

The ankyrin (ANK) gene cluster is a part of a multigene family encoding ANK transmembrane proteins in Arabidopsis thaliana, and plays an important role in protein–protein interactions and in signal pathways. In contrast to other regions of a genome, the ANK gene cluster exhibits an extremely high level of DNA polymorphism in an ∼5-kb region, without apparent decay. Phylogenetic analysis detects two clear, deeply differentiated haplotypes (dimorphism). The divergence between haplotypes of accession Col-0 and Ler-0 (Hap-C and Hap-L) is estimated to be 10.7%, approximately equal to the 10.5% average divergence between A. thaliana and A. lyrata. Sequence comparisons for the ANK gene cluster homologues in Col-0 indicate that the members evolve independently, and that the similarity among paralogues is lower than between alleles. Very little intralocus recombination or gene conversion is detected in ANK regions. All these characteristics of the ANK gene cluster are consistent with a tandem gene duplication and birth-and-death process. The possible mechanisms for and implications of this elevated nucleotide variation are also discussed, including the suggestion of balancing selection.

Background/Objectives Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. Subjects/Methods We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. Results We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53) Conclusions Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to

Full Text Available Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs in the EDN system could be associated with human obesity.We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex.We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63 and in the Hortega sample (p=0.001, OR=0.62. Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66 and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70. Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively. Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51 and rs3759475 (p=0.009, OR=0.53.Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic

Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53). Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.

Full Text Available Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP, thyroglobulin (TG and diacylglycerol O-acyltransferase (DGAT1. A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus, Canchim (5/8 Bos taurus + 3/8 Bos indicus, Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus, Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.

Athletic performance is a polygenic trait influenced by both environmental and genetic factors. Objective To investigate individually and in combination the association of common genepolymorphisms with athlete status in Ukrainians. Methods A total of 210 elite Ukrainian athletes (100 endurance-oriented and 110 power-orientated athletes) and 326 controls were genotyped for ACE I/D, HIF1A Pro582Ser, NOS3 –786 T/C, PPARA intron 7 G/C, PPARG Pro12Ala and PPARGC1B Ala203Pro genepolymorphisms, most of which were previously reported to be associated with athlete status or related intermediate phenotypes in different populations. Results Power-oriented athletes exhibited an increased frequency of the HIF1A Ser (16.1 vs. 9.4%, P = 0.034) and NOS3 T alleles (78.3 vs. 66.2%, P = 0.0019) in comparison with controls. Additionally, we found that the frequency of the PPARG Ala allele was significantly higher in power-oriented athletes compared with the endurance-oriented athletes (24.7 vs. 13.5%; P = 0.0076). Next, we determined the total genotype score (TGS, from the accumulated combination of the three polymorphisms, with a maximum value of 100 for the theoretically optimal polygenic score) in athletes and controls. The mean TGS was significantly higher in power-oriented athletes (39.1 ± 2.3 vs. 32.6 ± 1.5; P = 0.0142) than in controls. Conclusions We found that the HIF1A Ser, NOS3 T and PPARG Ala alleles were associated with power athlete status in Ukrainians. PMID:24744483

Full Text Available BACKGROUND: Graves' orbitopathy (GO as well as Graves' disease (GD hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR. GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age, for whom environmental effects had less time to influence outcomes than in adults. METHODS: 768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2. Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4 and lymphoid protein tyrosine phosphatase (PTPN22. RESULTS: The rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole. CONCLUSIONS: Allele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients.

Full Text Available Athletic performance is a polygenic trait influenced by both environmental and genetic factors. Objective: to investigate individually and in combination the association of common genepolymorphisms with athlete status in Ukrainians. Methods: A total of 210 elite Ukrainian athletes (100 endurance-oriented and 110 power-orientated athletes and 326 controls were genotyped for ACE I/D, HIF1A Pro582Ser, NOS3 –786 T/C, PPARA intron 7 G/C, PPARG Pro12Ala and PPARGC1B Ala203Pro genepolymorphisms, most of which were previously reported to be associated with athlete status or related intermediate phenotypes in different populations. Results: Power-oriented athletes exhibited an increased frequency of the HIF1A Ser (16.1 vs. 9.420P = 0.034 and NOS3 T alleles (78.3 vs. 66.220P = 0.0019 in comparison with controls. Additionally, we found that the frequency of the PPARG Ala allele was significantly higher in power-oriented athletes compared with the endurance-oriented athletes (24.7 vs. 13.520P = 0.0076. Next, we determined the total genotype score (TGS, from the accumulated combination of the three polymorphisms, with a maximum value of 100 for the theoretically optimal polygenic score in athletes and controls. The mean TGS was significantly higher in power-oriented athletes (39.1 ± 2.3 vs. 32.6 ± 1.5; P = 0.0142 than in controls. Conclusions: We found that the HIF1A Ser, NOS3 T and PPARG Ala alleles were associated with power athlete status in Ukrainians.

Full Text Available Abstract Background The advent of high throughput sequencing technology has enabled the 1000 Genomes Project Pilot 3 to generate complete sequence data for more than 906 genes and 8,140 exons representing 697 subjects. The 1000 Genomes database provides a critical opportunity for further interpreting disease associations with single nucleotide polymorphisms (SNPs discovered from genetic association studies. Currently, direct sequencing of candidate genes or regions on a large number of subjects remains both cost- and time-prohibitive. Results To accelerate the translation from discovery to functional studies, we propose an in silico gene sequencing method (ISS, which predicts phased sequences of intragenic regions, using SNPs. The key underlying idea of our method is to infer diploid sequences (a pair of phased sequences/alleles at every functional locus utilizing the deep sequencing data from the 1000 Genomes Project and SNP data from the HapMap Project, and to build prediction models using flanking SNPs. Using this method, we have developed a database of prediction models for 611 known genes. Sequence prediction accuracy for these genes is 96.26% on average (ranges 79%-100%. This database of prediction models can be enhanced and scaled up to include new genes as the 1000 Genomes Project sequences additional genes on additional individuals. Applying our predictive model for the KCNJ11 gene to the Wellcome Trust Case Control Consortium (WTCCC Type 2 diabetes cohort, we demonstrate how the prediction of phased sequences inferred from GWAS SNP genotype data can be used to facilitate interpretation and identify a probable functional mechanism such as protein changes. Conclusions Prior to the general availability of routine sequencing of all subjects, the ISS method proposed here provides a time- and cost-effective approach to broadening the characterization of disease associated SNPs and regions, and facilitating the prioritization of candidate

Human blood plasma/sera are classified into three distinct vitronectin types based on the relative amount of the 75 kDa polypeptide to its cleavage product of 65 kDa. We asked whether the vitronectin blood types correlated with the polymorphism of the vitronectin gene. A portion of the vitronectin gene was amplified by using polymerase chain reaction and digested with a restriction enzyme PmaC I which may distinguish the base sequence causing the polymorphic change at the amino acid position 381. Amplified DNAs of the blood type I (75 kDa-rich), II (75/65 kDa-even), and III (65 kDa-rich) were shown to be resistant, moderately sensitive and completely sensitive to PmaC I, respectively. These results suggest that Thr at position 381 is essential for the cleavage of the vitronectin 75 kDa polypeptide and that three possible combinations of two codominant alleles of vitronectin determine three vitronectin blood types.

Full Text Available Nicotine is a major addictive compound in tobacco cigarette smoke. After being absorbed by the lung nicotine is rapidly metabolized and mainly inactivated to cotinine by hepatic cytochrome P450 2A6 (CYP2A6 enzyme. Genetic polymorphisms in CYP2A6 may play a role in smoking behavior and nicotine dependence. CYP2A6*1A is the wild type of the CYP2A6 gene which is associated with normal or extensive nicotine metabolism. In the CYP2A6 gene, several polymorphic alleles have been reported such as CYP2A6*4, CYP2A6*7, CYP2A6*9, and CYP2A6*10 which are related to decreasing nicotine metabolism activity. The variation of nicotine metabolism activity could alter nicotine plasma levels. Smokers need a certain level of nicotine in their brain and must smoke regularly because of nicotine’s short half-life; this increases the number of smoked cigarettes in extensive metabolizers. Meanwhile, in slow metabolizers, nicotine plasma level may increase and results in nicotine toxicity. This will eventually lower the risk of dependence. (Med J Indones 2010; 19:46-51Keywords: cotinine, hepatic cytochrome P450 2A6, smoking behavior

Full Text Available The APOBEC3 gene family plays a role in innate cellular immunity inhibiting retroviral infection, hepatitis B virus propagation, and the retrotransposition of endogenous elements. We present a detailed sequence and population genetic analysis of a 29.5-kb common human deletion polymorphism that removes the APOBEC3B gene. We developed a PCR-based genotyping assay, characterized 1,277 human diversity samples, and found that the frequency of the deletion allele varies significantly among major continental groups (global FST = 0.2843. The deletion is rare in Africans and Europeans (frequency of 0.9% and 6%, more common in East Asians and Amerindians (36.9% and 57.7%, and almost fixed in Oceanic populations (92.9%. Despite a worldwide frequency of 22.5%, analysis of data from the International HapMap Project reveals that no single existing tag single nucleotide polymorphism may serve as a surrogate for the deletion variant, emphasizing that without careful analysis its phenotypic impact may be overlooked in association studies. Application of haplotype-based tests for selection revealed potential pitfalls in the direct application of existing methods to the analysis of genomic structural variation. These data emphasize the importance of directly genotyping structural variation in association studies and of accurately resolving variant breakpoints before proceeding with more detailed population-genetic analysis.

Full Text Available Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p > 0.05 in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus.

The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D genepolymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

Alcohol-related diseases cause significant harm in the western world. Up to 65 % of the phenotypic variance is genetically determined. Few candidate genes have been identified, comprising ADH4, ALDH2, COMT, CRHR1, DAT (SLC6A3), GABRA2 and MAOA. While abnormalities in the dopaminergic mesolimbic reward system are considered important mediators of alcoholism, studies analyzing variants of dopamine receptors showed conflicting results. Other modulators of the reward system are synaptosomal genes. Among candidate genes, polygenic variants of the Vesicular Monamine Transporter 2 (VMAT2) gene locus associated with alterations of drinking behavior were published. These variants comprise single nucleotide polymorphisms (SNPs) within the promoter region and the open reading frame. In this study, we confirm the association of VMAT2 SNP rs363387 (allelic association: p = 0.015) with alcohol dependence. This SNP defines several haplotypes including up to four SNPs (minimal p = 0.0045). In addition, numeric effects in the subgroups of males and patients with positive family history were found. We suggest that several rs363387 T-allele containing haplotypes increase the risk of alcohol dependence (OR 1.53), whereas G-allele containing haplotypes confer protection against alcohol dependence. Taken together, there is supporting evidence for a contribution of VMAT2 gene variants to phenotypes of alcohol dependence.

Poly (ADP-ribose) polymerase-1 (PARP-1) can exacerbate ischemic brain injury and lessen ischemic neuronal death, which may be associated with PARP-1 polymorphisms. The present study investigated human PARP-1 genepolymorphisms in various Chinese nationalities, the results of which could potentially help in the treatment and prevention of neurologic diseases. Genetic polymorphisms of seven exons in the PARP-1 gene, in 898 Chinese Han, Buyi, Shui, Miao, and Zhuang subjects, were investigated by PCR-single-strand conformation polymorphism. A single-strand conformation polymorphism variant in exons 12, 13, 16, and 17 of the PARP-1 gene was identified in 148 people, with two stationary bands showing three degenerative single strands.Results showed that the PARP-1 genepolymorphisms exist in various nationalities, and may act as a biomarker for susceptibility to disease.

Objective To evaluate the status of eight RHD specific exons in 131 Han Chinese blood donors who were classified as RhD-negative by serological methods and explore the genomic structure of RHD gene among the Han Chinese. The Rh blood group system has the highest prevalence of polymorphisms among human blood group systems and is clinically significant in transfusion medicine. The Rh antigens are expressed on polypeptides encoded by two highly homologous genes, RHD and RHCE. Recent molecular studies have shown that the RhD-negative trait could be generated by multiple genetic mechanisms and is ethnic group-dependent.Methods The polymerase chain reaction using-sequence specific primers (PCR-SSP) was used to amplify exons 2, 3, 4, 5, 6, 7, 9 and 10 of RHD gene and exons 1, 2 and 5 of RHCE gene, as well as intron 4 in each of them.Results The 131 cases of RhD-negative phenotypes consisted of 60 ccee, 58 Ccee, 5 ccEe, 5 CcEe and 3 CCee. Among them, 83 with the Rh ccee or ccEe phenotypes (63.4%) lacked the eight RHD exons indicated above, while 26 cases with the Rh Ccee, CCee, CcEe phenotypes (19.9%) had all the RHD exons examined. Twenty-two individuals with the Ccee, CCee, CcEe phenotypes (16.8%) carried at least one RHD exon. The phenotypes of the RhD negative individuals carrying the RHD gene were Rh CC or Cc, but not cc. Conclusions Three classes of RhD-negative polymorphisms among a population of Han Chinese were observed. Antigen association analysis suggested the existence of a novel class of RhD-negative associated haplotype in Han Chinese. This haplotype consisted of a normal RHCE allele and a nonfunctional RHD gene. It may be beneficial to redefine the RhD-negative blood group among Chinese populations upon clarification of the mechanisms of RHD gene expression and RhD antigen immunization.

Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA) genepolymorphism (rs2234693-PvuII) (T→C substitution) and oxytocin receptor genepolymorphism (rs53576) (G→A substitution) with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20-25 years of age, sexually active, with normal menstrual cycles (28-35 days), were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs), polycystic ovary syndrome (PCOS), thyroid diseases as well as drugs that are implicated in hypothalamus-pituitary-gonadal axis. T allele (wildtype) of rs2234693 (PvuII) polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic) of rs53576 (OXTR) polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII) and A allele of rs53576 (OXTR) polymorphisms (T + A group) was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

Full Text Available Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA genepolymorphism (rs2234693-PvuII (T→C substitution and oxytocin receptor genepolymorphism (rs53576 (G→A substitution with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days, were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs, polycystic ovary syndrome (PCOS, thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype of rs2234693 (PvuII polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic of rs53576 (OXTR polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII and A allele of rs53576 (OXTR polymorphisms (T + A group was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

Aflatoxin B1 (AFB1) is an important environmental carcinogen and can induce DNA damage and involve in the carcinogenesis of hepatocellular carcinoma (HCC). The deficiency of DNA repair capacity related to the polymorphisms of DNA repair genes might play a central role in the process of HCC tumorigenesis. However, the interaction of DNA repair genepolymorphisms and AFB1 in the risk of hepatocellular carcinoma has not been elucidated. In this study, we investigated whether six polymorphisms (i...

Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn’s disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn’s disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn’s disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies. PMID:28052094

Background Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE genepolymorphism in patients with kidney disease who were in a tr

Conclusions: Taken together, our findings demonstrated that IL-10 promoter genepolymorphism (−1082 and −819 may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine genepolymorphisms will lead to a better understanding of the disease’s biological background.

Conclusion: Findings of this study suggest that ACE and CYP46A1 genespolymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genespolymorphism as a marker of susceptibility to senile cataract needs further validation in studies involving larger number of patients from different regions.

Background Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE genepolymorphism in patients with kidney disease who were in a

Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage.

Full Text Available Abstract Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. Results We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. Conclusion The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

In this study, we investigated the role of the -174G>C polymorphism of interleukin-6 (IL-6) as a predisposing factor to angina pectoris. Patients were separated into 2 groups: angina (N = 72) and nonangina (N = 71). There were no statistical differences between groups for all cardiovascular risk factors evaluated. The GG genotype frequency was 18% lower in the angina than in the non-angina group, whereas GC + CC was 18% higher in the angina group (P = .036). The frequency of G allele was 11% lower in the angina than in the nonangina group and C allele was 11% higher in the angina group (P = .043). Patients carrying the C allele showed a 2-fold increased risk for angina pectoris (P = .036). Our study demonstrates a high incidence of the -174G>C polymorphism of the IL-6 gene in patients with angina pectoris compared with those carrying the G allele, reinforcing the contribution of genetic factors to the symptoms of angina pectoris.

Dilated Cardiomyopathy (DCM) is characterized by systolic dysfunction, followed by heart failure necessitating cardiac transplantation. The genetic basis is well established by the identification of mutations in sarcomere and cytoskeleton gene/s. Modifier genes and environmental factors are also considered to play a significant role in the variable expression of the disease, hence various mechanisms are implicated and one such mechanism is oxidative stress. Nitric Oxide (NO), a primary physiological transmitter derived from endothelium seems to play a composite role with diverse anti-atherogenic effects as vasodilator. Three functional polymorphisms of endothelial nitric oxide synthase (NOS3) gene viz., T-786C of the 5′ flanking region, 27bp VNTR in intron4 and G894T of exon 7 were genotyped to identify their role in DCM. A total of 115 DCM samples and 454 controls were included. Genotyping was carried out by PCR -RFLP method. Allelic and genotypic frequencies were computed in both control & patient groups and appropriate statistical tests were employed. A significant association of TC genotype (T-786C) with an odds ratio of 1.74, (95% CI 1.14 - 2.67, p = 0.01) was observed in DCM. Likewise the GT genotypic frequency of G894T polymorphism was found to be statistically significant (OR 2.10, 95% CI 1.34–3.27, p = 0.0011), with the recessive allele T being significantly associated with DCM (OR 1.64, 95% CI 1.18 - 2.30, p = 0.003). The haplotype carrying the recessive alleles of G894T and T-786C, C4bT was found to exhibit 7 folds increased risk for DCM compared to the controls. Hence C4bT haplotype could be the risk haplotype for DCM. Our findings suggest the possible implication of NOS3 gene in the disease phenotype, wherein NOS3 may be synergistically functioning in DCM associated heart failure via the excessive production of NO in cardiomyocytes resulting in decreased myocardial contractility and systolic dysfunction, a common feature of DCM

Full Text Available Dilated Cardiomyopathy (DCM is characterized by systolic dysfunction, followed by heart failure necessitating cardiac transplantation. The genetic basis is well established by the identification of mutations in sarcomere and cytoskeleton gene/s. Modifier genes and environmental factors are also considered to play a significant role in the variable expression of the disease, hence various mechanisms are implicated and one such mechanism is oxidative stress. Nitric Oxide (NO, a primary physiological transmitter derived from endothelium seems to play a composite role with diverse anti-atherogenic effects as vasodilator. Three functional polymorphisms of endothelial nitric oxide synthase (NOS3 gene viz., T-786C of the 5' flanking region, 27bp VNTR in intron4 and G894T of exon 7 were genotyped to identify their role in DCM. A total of 115 DCM samples and 454 controls were included. Genotyping was carried out by PCR -RFLP method. Allelic and genotypic frequencies were computed in both control & patient groups and appropriate statistical tests were employed. A significant association of TC genotype (T-786C with an odds ratio of 1.74, (95% CI 1.14 - 2.67, p = 0.01 was observed in DCM. Likewise the GT genotypic frequency of G894T polymorphism was found to be statistically significant (OR 2.10, 95% CI 1.34-3.27, p = 0.0011, with the recessive allele T being significantly associated with DCM (OR 1.64, 95% CI 1.18 - 2.30, p = 0.003. The haplotype carrying the recessive alleles of G894T and T-786C, C4bT was found to exhibit 7 folds increased risk for DCM compared to the controls. Hence C4bT haplotype could be the risk haplotype for DCM. Our findings suggest the possible implication of NOS3 gene in the disease phenotype, wherein NOS3 may be synergistically functioning in DCM associated heart failure via the excessive production of NO in cardiomyocytes resulting in decreased myocardial contractility and systolic dysfunction, a common feature of DCM

Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type...... 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different...... countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found...

Idiopathic granulomatous mastitis (IGM) is a rare and chronic inflammatory disorder. IGM mimics breast cancer regarding its clinical and radiological features. Etiology of IGM remains unclarified. Our patient was 37-year-old and 14 weeks pregnant. There was pain, redness and swelling in the right breast. The mass suggestive of malignancy was detected in sonography. Serum CA 125 and CA 15-3 levels were high. Genetic analysis was performed for the etiology. methylenetetrahydrofolate reductase (MTHFR) C 677 TT, β-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 5 G/5 G, angiotensin-converting enzyme (ACE) I/D mutation was found. IGM was diagnosed by cor biopsy. An association was also reported between breast cancer and mutations in MTHFR-C 677 T, PAI-1, ACE genes. Genetic polymorphisms may involve in the development of IGM as it was seen in our case. Further studies should be conducted to better clarify this plausible association. PMID:27619324

Matrix gamma-carboxy glutamic acid protein (MGP) is a 10-kDa secreted protein containing five residues of the vitamin K-dependent calcium binding amino acid gamma-carboxyglutamic acid (Gla). This study was carried out to examine the effects of MGP gene promoter polymorphism (T-138C) on blood lead levels (BLL) and hematological parameters in 113 battery manufacturing unit workers occupationally exposed to lead and 102 controls. Genotypes for the MGP T-138C polymorphism were determined by PCR and restriction fragment length digestion. BLL were determined by Anode Stripping Voltammetry using ESA Model 3010B Lead analyzer. Complete blood picture (CBP) was analyzed using ADVIA Cell counter for each sample. The frequencies of MGP-TT, CT and CC genotypes in our population were 38.6%, 44.3%, and 17.2%, respectively. The frequencies for T and C alleles were 0.612 and 0.386, respectively. Although BLL did not differ significantly among genotypes; they were higher in workers with TT/CT genotype compared to CC genotype subjects (76-88 microg/dL vs 22-45 microg/dL, p > 0.05). About 29.2% of volunteers (n = 33) from the occupationally exposed group had hemoglobin levels below 10.0 gms/dl. There was no significant difference in total white cell count and platelet count between occupational and non-exposed groups. The possible role of SNPs in the promoter region of MGP gene with relation to lead toxicity was investigated for the first time in the Indian population; although significance could not be achieved in this study, further assessments over a larger population size may help in better understanding of the consequences of lead exposure.

Full Text Available Psoriasis is associated with cutaneous and systemic overexpression of several proinflammatory cytokines. The aim of this study was to investigate the relationship between susceptibility to psoriasis and polymorphisms of tumor necrosis factor alpha (TNF-α, interferon gamma (INF-γ, interleukin (IL-10, IL-6 and transforming growth factor beta (TGF-β. Eighty-nine patients with psoriasis and 201 healthy controls were enrolled into the study. The patient group was divided into 2 subgroups as early-onset (group 1 and late-onset (group 2. The cytokine genepolymorphisms in each group were determined by polymerase chain reaction-single specific primer. When the whole and only group 1 patients were compared with the controls, TGF-β TT/GC genotype was significantly high in the whole and group 1 patients. When we compared the group 1 and group 2, the frequency of IFN-γ AA genotype was found to be significantly high in group 1 which lost significance after Bonferroni correction. Patients with moderate symptoms had a significantly high frequency of IL-10 GCC/GCC genotype that did not remain significant after correction. These data from our small group of patients demonstrated that the only significant difference between the whole patient group and the controls was for TGF-β TT/GC genotype with a higher frequency in the patients. Due to the involvement of many other genes relating to the activity of Th1 cytokines, further studies are required to determine the molecular basis of the susceptibility to psoriasis.

Full Text Available To investigate the role of the reninangiotensin system genespolymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

Sarcoidosis is a systemic inflammatory disease of unknown etiology. Osteopontin (SPP1, OPN) is an extra cellular matrix glycoprotein and cytokine with a known role in granuloma formation and in autoimmune and inflammatory diseases. To determine whether plasma OPN levels are elevated in patients with sarcoidosis and compare the frequency of four single nucleotide polymorphism (SNPs) variants in the OPN gene in sarcoidosis patients compared to healthy controls. Demographic and clinical information, radiological studies and pulmonary function tests were evaluated in 113 patients with sarcoidosis and in 79 healthy controls. Blood samples were analyzed for SNPs of the OPN gene and for plasma OPN and CRP levels. Association between clinical features of disease and OPN levels as well as SNP frequencies was determined. Plasma OPN levels were higher in sarcoidosis patients than in healthy subjects, (median: 217 vs 122ng/ml, psarcoidosis patients and controls in the frequency of any of the SNPs evaluated. Presence of lung parenchymal involvement was associated with SNP distribution at rs1126772 (p = 0.02). We found no correlation between SNPs distribution and plasma OPN levels. Osteopontin protein levels are elevated in sarcoidosis. We found no evidence for an association between SNPs on the osteopontin gene and plasma OPN levels or the presence of sarcoidosis, however, an association between genotype and several phenotypic clinical parameters of disease was observed.

Psoriasis is a common inflammatory skin disease with an etiology bases on both environmental and genetic factors. As is the case of many autoimmune diseases its real cause remains poorly defined. However, it is known that genetic factors contribute to disease susceptibility. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Some other studies have focused upon single nucleotide polymorphisms (SNPs) for mapping of probable causal variants. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. CNVs represent an important element of genomic polymorphism in humans and harboring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. The mechanisms giving rise to SNPs and CNVs can be considered as fundamental processes underlying gene duplications, deletions, insertions, inversions and complex combinations of rearrangements. The duplicated genes being the results of 'successful' copies are fixed and maintained in the population. Conversely, many 'unsuccessful' duplicates remain in the genome as pseudogenes. There is another form of genetic variations termed copy-neutral loss of heterozygosity (LOH) with less information about their potential impact on complex diseases. Additional studies would include associated gene expression variations with either SNPs or CNVs. Now many genetic techniques such as PCR, real time PCR, microarray and restriction fragment length analysis are available for detecting genetic polymorphisms, gene mapping and estimation of gene expression. Recently, the scientists have used these tools to define genetic signatures of disease, to understand genetic causes of disease and to characterize the effects of certain drugs on gene expression. This review highlights the principles, technology and applications on

The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility. This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group. Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 genepolymorphisms did not show statistical significance, nor did the AMHR2 genepolymorphism. However, the AMH genepolymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis. We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the - 482A G SNP in the AMHR2 gene were found to be unrelated.

Background Inflammatory genepolymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory genepolymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. Methods We recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene pol...

Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...

Introduction: cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine genepolymorphism in Romanian multiple myeloma patients. Material and methods: cytokine genotyping was performed in 80...

Nephropathy is an important and a frequent complication of long-term type II diabetic nephropathy. Strong evidence exists that genetic predisposition plays a major role in the development of diabetic nephropathy. Recent studies have implicated association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) genepolymorphism and nephropathy. The deletion genepolymorphism of ACE gene has been shown to be associated with increased activity of this enzyme. This study examines th...

Gastric cancer(GC) is the third leading cause of cancerrelated death worldwide.In areas of high prevalence,such as Japan,South Korea and China,most cases of GC are related to Helicobacter pylori(H.pylori),which involves well-characterized sequential stages,including infection,atrophic gastritis,intestinal metaplasia,dysplasia,and GC.Mucins are the most abundant highmolecular-weight glycoproteins in mucus,which is the first line of defense and plays a major role in blocking pathogenic factors.Normal gastric mucosa shows expression of MUC1,MUC5 AC and MUC6 that is specific to cell type.However,the specific pattern of MUC1,MUC5 AC and MUC6 expression is changed in gastric carcinogenesis,accompanied by de novo expression of secreted MUC2.Recent studies have provided evidence that variations in these mucin genes affect many steps of GC development,such as H.pylori infection,and gastric precancerous lesions.In this review,we focus on studies of the association between polymorphisms in mucin genes and development of GC.This information should be helpful for the early detection,surveillance,and treatment of GC.

The human epsilon-globin gene is necessary for primitive human erythropoiesis in the yolk sac. Herein we report a non-radioactive single-strand conformation polymorphism (SSCP) approach to screen the human epsilon-globin gene and its regulatory regions for possible mutations and single-nucleotide polymorphisms in normal adult subjects, in order to determine those genomic regions, which are not necessary for its proper regulation and function. We identified no sequence variations apart from the expected 5'epsilon /HincII polymorphism in the fragments analyzed, suggesting that genomic alterations in the epsilon-globin gene are most likely incompatible with normal erythropoiesis and proper embryonic development.

Full Text Available The objectives of the research were to detect DNA polymorphism at locus 2 of bovine growth hormone gene of Madura cattle and to know its genetic diversity. DNA polymorphisms and their effect on phenotypic traits have been studied widely in dairy cattle but not for beef cattle, especially for Indonesian local cattle. Polymorphism was detected using PCR-RFLP using primer GH-5 and GH-6 for amplifying locus 2 of growth hormone gene. Genetic diversity was analyzed based on the formula of Nei (1973, 1975. DNA polymorphism was found on locus 2 of growth hormone gene using MspI restriction enzyme. This polymorphism may be caused the lost of restriction MspI site. The genetic diversity was 0.4422.

Background Sarcoidosis is a systemic inflammatory disease of unknown etiology. Osteopontin (SPP1, OPN) is an extra cellular matrix glycoprotein and cytokine with a known role in granuloma formation and in autoimmune and inflammatory diseases. Objective To determine whether plasma OPN levels are elevated in patients with sarcoidosis and compare the frequency of four single nucleotide polymorphism (SNPs) variants in the OPN gene in sarcoidosis patients compared to healthy controls. Methods Demographic and clinical information, radiological studies and pulmonary function tests were evaluated in 113 patients with sarcoidosis and in 79 healthy controls. Blood samples were analyzed for SNPs of the OPN gene and for plasma OPN and CRP levels. Association between clinical features of disease and OPN levels as well as SNP frequencies was determined. Results Plasma OPN levels were higher in sarcoidosis patients than in healthy subjects, (median: 217 vs 122ng/ml, p<0.001). Area under the curve for receiver operator curves (ROC) was 0.798 (0.686–0.909 95% CI.) No differences were observed between sarcoidosis patients and controls in the frequency of any of the SNPs evaluated. Presence of lung parenchymal involvement was associated with SNP distribution at rs1126772 (p = 0.02). We found no correlation between SNPs distribution and plasma OPN levels. Conclusions Osteopontin protein levels are elevated in sarcoidosis. We found no evidence for an association between SNPs on the osteopontin gene and plasma OPN levels or the presence of sarcoidosis, however, an association between genotype and several phenotypic clinical parameters of disease was observed. PMID:28253271

Full Text Available Purpose: Several genes encoding different cytokines and human leucocyte antigens (HLA may play crucial roles in host susceptibility to tuberculosis (TB. Our objective was to investigate whether these genes might be associated with protection from or susceptibility to TB. Materials and Methods: Genomic DNA from patients with TB (n = 30 and ethnically matched controls (n = 30 was genotyped by using sequence-specific primers-polymerase chain reaction and sequence-specific oligonucletid methods. Results: Our results demonstrated that HLA-CwFNx0101 [P = 0.05, odds ration (OR (95% confidence interval = 2.269 (1.702-3.027] allele frequency was significantly more common in TB patients than in healthy controls, and HLA-CwFNx0101 may be associated with susceptibility to TB. Analysis of cytokine allele frequencies showed that interleukin (IL-10, -819 C and -592 C alleles was significantly more common in TB patients than in controls (pc: 0.038 and 0.017, respectively. From the IL-10 cluster, a positive significant difference was found at positions -1082 and -592 C/C (pc: 0.027 and 0.054, respectively genotypes. Although these differences could be explained by the highest frequency of C/C and G/G homozygous patients with TB, in contrast to the control group, statistically significant differences for the C/C genotype however were lost after Bonferroni correction of the P-values. Conclusion: Altogether, our results suggest that the polymorphisms in HLA (class I and cytokine (IL-10 genes may affect the susceptibility to TB and increase the risk of developing the disease.

Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus （T2DM）. The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. Among the recognized markers are interleukin（IL）-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha（TNF-α）, C-reactive protein, resistin, adiponectin, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms（SNPs） in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

Full Text Available Abstract Background The human NOTCH4 gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiological roles. In a British linkage study, NOTCH4 genepolymorphisms were highly associated with schizophrenia. In a Japanese case-control association study, however, these polymorphisms did not show significant associations with schizophrenia. We conducted a case-control study with Japanese subjects to explore an association between the triplet repeat polymorphism in the NOTCH4 gene and schizophrenia, including subtypes of schizophrenia, longitudinal disease course characteristics, and a positive family history for psychoses. Methods We examined the (CTGn repeat polymorphism in the NOTCH4 gene among 100 healthy Japanese individuals and 102 patients with schizophrenia (22 paranoid, 38 disorganized, 29 residual, 64 episodic, 31 continuous, 42 with prominent negative symptoms, and 46 with positive family histories using a polymerase chain reaction-based, single-strand conformational polymorphism analysis. Results Five different alleles consisting of 6, 9, 10, 11, and 13 repeats of CTG (Leu in patients with schizophrenia, and 4 alleles consisting of 6, 9, 10, and 11 repeats in controls were found. No significant differences in genotype or allele frequencies of repeat numbers were found between controls and patients. In addition, there were no associations between the polymorphism and schizophrenia subtypes, longitudinal disease course characteristics, or positive family history of the patients. Conclusions Our data suggest a lack of association between the NOTCH4 gene triplet repeat polymorphism and schizophrenia in Japanese individuals.

Objective To assess the genespolymorphisms associated with intracerebral hemorrhage(ICH)in Chinese quantitatively or qualitatively by searching all case control studies related comprehensively.Methods Odds ratio(OR)and 95%confidence intervals(95%CI)were determined for each polymorphism using fixed or random model with Revman 5.1.Results Statistically significant associations with ICH were

OBJECTIVE: To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness. DESIGN AND METHODS: The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and

Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the…

PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

In recent years a vast amount of data has been published on the association between the insertion/deletion (VD) polymorphism of the gene coding for angiotensin-converting enzyme and renal disease. It has be come clear that the polymorphism does not affect the prevalence of renal disease. However, da

We concluded that the prevalence of FV (G1691A and A4070G and PAI-1 4G/5G polymorphisms increased the risk of DVT occurrence in subjects. These findings provide additional evidence to support the hypothesis that thrombophilic genepolymorphisms are involved in vascular thromboembolism.

proteins in this system predict risk of atrial fibrillation. METHODS AND RESULTS: We genotyped 9235 individuals from the Danish general population, The Copenhagen City Heart Study, for the a-20c, g-6a, T174M, and M235T polymorphisms in the angiotensinogen gene and the insertion/deletion (I/D) polymorphism...

Objective To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5 -hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS);and to investigate the im-

Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU). To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility. Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects. Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects. Polymorphisms in IL21 may be associated with sepsis risk.

Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 polymorphism in Parakanã Indians and found a lack of this polymorphism in the Parakanã population.

To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene's promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.

Single nucleotide polymorphisms (SNPs) in the Reelin gene (RELN) are likely candidates to confer risk for autism. The objective of the present study is to investigate the association of RELN gene SNPs with autism. A total of 367 Chinese Han subjects were recruited, including 186 autism patients and 181 unrelated healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to detect RELN genepolymorphisms. The association between SNPs and autism was analyzed in this study. The g.333509A>C in intron12 and g.504742G>A in exon60 were detected in the RELN gene and a significant association was found between the g.504742G>A polymorphism and autism. Allele and genotype frequencies for the g.504742G>A polymorphism in autistic patients were significantly different for healthy subjects. There was no significantly difference in g.333509A>C polymorphism and autism in the studied populations. Our findings indicated that g.333509A>C was not significantly associated with autism. The g.504742G>A polymorphic variant in the RELN gene might affect subjects susceptibility toward autism in Chinese Han population.

Full Text Available DNA sequencing is the most conclusive method for emm (M protein gene typing of Streptococcus pyogenes. This method is not a feasible approach in developing countries where streptococcal infection is widespread among adults and children. Alternatively the PCR-RFLP has the potential for rapid screening of different types of S. pyogenes. To document the emm type distribution of S. pyogenes in a group of patients suffering from pharyngitis, the restriction fragment length polymorphism (RFLP profile of 50 isolates were analyzed. By using Hae III+ HincII (double digestion and Dde I restriction enzymes and based on RFLP, the profile patterns of the isolates were compared. The analysis of data identified 15 distinct RFLP patterns for Hae III+ Hinc II and 13 patterns for Dde I. They differ from each other by at least one band. Although the number of isolates was not sufficient to make any epidemiological conclusion, but the finding demonstrated that the S. pyogenes population among pateints was heterogeneous. Regarding the PCR method, we managed to improve the results by modification of CDC protocol in three different ways. This study was conducted in normal circumstances when pharyngitis was at the peak seasonal incident. However emm amplicon restriction digest analysis is a valuable tool for rapid analysis of S. pyogenes infection in more important situation like outbreaks and in selected type of study like consideration of nosocomial infection.

Phenotypic evidence indicates that the ability to taste the bitter compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against cigarette smoking. In this study, PTC gene haplotypes were found to be associated with both the odds of being a smoker and the importance of cigarette taste as a smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV haplotype, relative to the "nontaster" AVI haplotype, was predicted to be associated with reduced odds of being a smoker and lower taste motivation as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 taste/sensory processes scale. The results did not support the predicted association between the PAV and AVI haplotypes and smoker odds, but the AAV haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated with reduced smoker prevalence (49% vs. 70%), chi(2)(1, N = 567) = 10.392, p = .001. The predicted relationship between PAV and AVI and taste motivation was found, F(2, 348) = 3.303, p = .038. The results encourage further exploration of the role of taste/sensory processes in tobacco dependence.

The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism ofirrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Genepolymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 genepolymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair genepolymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR genepolymorphism in intron 1 contains a polymorphic single sequence dinudeotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity

Full Text Available The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Genepolymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 genepolymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair genepolymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR genepolymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR

The Glu298Asp genepolymorphism in NOS3 gene has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NOS3 Glu298Asp polymorphism and AD risk by using meta-analysis. All eligible case-control studies were searched in PubMed and Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to assess the association. A total of 5522 cases and 4877 controls in 20 case-control studies were included. Obvious heterogeneity among studies was detected, and no significant association was observed between the NOS3 Glu298Asp polymorphism and AD risk. After exclusion of three studies, the heterogeneity disappeared and still no association was observed. In the subgroup analysis by ethnicity, we did not find any significant association between this polymorphism and AD risk in both Asians and Caucasians. This meta-analysis suggested that the NOS3 Glu298Asp genepolymorphism is not a strong risk factor for AD. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of NOS3 gene and AD risk, more studies with large groups of patients are required.

May 26, 2016 ... Conclusion: Our results suggest that TLR4 genepolymorphism is not a key modulator of the risk ... regulators in maintaining the balance between commensal ..... mation, and energy-related factors: a novel pathway of cancer.

Full Text Available The androgen receptor (AR genepolymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR genepolymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa--the Hadza (monogamous foragers and the Datoga (polygynous pastoralists. We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17-70 years. We conducted structural equation modeling to identify links between AR genepolymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born.

Objective To investigate the influence of vitamin D receptor (VDR) genepolymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population.Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI.Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P=0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms.Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Hah population of Beijing.

Conclusion: Our data suggested that polymorphisms in the IL-27 gene may not contribute to HBV susceptibility. Further studies with large sample size should be conducted to validate these results in Egyptian population.

The androgen receptor (AR) genepolymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR genepolymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR genepolymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born. PMID:26291982

Objective To investigate the association of single nucleotide polymorphisms(SNPs)of the mannan-binding lectin(MBL)gene with serum levels,development,progression and prognosis of severe lupus nephritis(LN).Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October2013.Integrated capillary electrophoresis was used to detect MBL genepolymorphism in peripheral blood

Objective: A number of studies have investigated the relationship between the PON1 genepolymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 genepolymorphisms and breast cancer risk. Methods: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Informati...

AIM: To assess the relationship between vitamin D re-ceptor (VDR) genepolymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucle-otide genepolymorphisms of the VDR w...

To investigate the prevalence of the p27 genepolymorphism in women with endometriosis. Transversal case-control study. Genomic DNA was extracted from cells collected from buccal swabs. The p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population. We analysed the 104 patients and 109 control subjects. The distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p=0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR=1.9; 95% CI, 1.120-3.343). The polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development.

Full Text Available Vitamin D receptor (VDR genepolymorphisms have been suggested as possible determinants of bone mineral density (BMD and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR genepolymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p = 0.08. Also no association between biochemical data and VDR genepolymorphisms was observed.

Full Text Available We studied the prevalence of polymorphisms in genes XRCC2 and XRCC3 in stomach cancer patients who lived in North Eastern Turkey. A total of 61 cancer patients and 78 controls were included in this study. Single nucleotide changes were studied in XRCC2 and XRCC3 genes at locus Arg188His and Thr241Met. Blood samples were taken from the patients and controls, and DNA was isolated. The regions of interest were amplified using a polymerase chain reaction method. After amplification, we used restriction enzymes (HphI and NcoI to digest the amplified product. Digested product was then run through gel electrophoresis. We identified changes in the nucleotides in these specific regions. It was found that the Arg188His polymorphism of the XRCC2 gene was about 39% (24 out of the 61 among cancer patients. However, only 15% (12 out of 78 of the control group indicated this polymorphism. We also observed that 18 of the 61 cancer patients (29% carried the Thr241Met polymorphism of the XRCC3 gene whereas 11 of the 78 (14% individuals in the control group had the polymorphism. Our results showed a significant difference in polymorphism ratios between the cancer patients and health control group for the regions of interest. This result clearly showed that these polymorphisms increase the risk of stomach cancer and might be a strong marker for early diagnosis of gastric cancer.

Full Text Available Objective To investigate the correlation between-572G/C and-174G/C polymorphism of IL-6 gene and sepsis of Chinese Han population in Henan province.Methods A population-based case-control study involving 99 patients with sepsis and 260 health volunteers(control was carried out.The-572C/G and-174G/C polymorphism of IL-6 gene was analyzed by polymerase chain reaction and restriction fragment-length polymorphism(PCR-RFLP technique.Results The genotype frequencies of all 359 cases were in Hardy-Weinberg equilibrium(P>0.05.No polymorphism was found in-174 site(GG genotype only,while alleles G,C and genotypes GG,GC,CC were found in-572 site,and no significant difference of allele frequency existed between patients and controls.Unconditional logistic regression analysis showed-G572C polymorphism was related to sepsis,the susceptibility to sepsis of patients with GG genotype was significantly higher than that of patients with CC genotype(OR=2.411,95% CI=1.045-5.562,P=0.039 after age and gender correction.Conclusions The-G572C polymorphism of IL-6 gene associates with sepsis,and the GG is the risk genotype of sepsis.There maybe no polymorphism in-G174C of IL-6 gene of Chinese Han population in Henan province.

The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group genepolymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 genepolymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P triglycerides in the Marshfield sample (P triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

Objectives Osteoprotegerin (OPG) has an important role in bone remodeling, and it has been proposed that the OPG gene might be a candidate gene for osteoporosis predisposition. Several studies have already assessed the connection between OPG genepolymorphism and bone mineral density (BMD). In this study we wanted to analyze the association of two polymorphisms in the OPG gene with BMD and bone turnover markers in women with and without osteoporosis. Material and methods In 22 postmenopausal women with osteoporosis (aged 65.6 ±12.6) and 59 women without osteoporosis (aged 60.8 ±8.7) we analyzed the association of two polymorphisms in the OPG gene with BMD, measured by dual energy absorptiometry and with bone turnover markers (crosslaps and osteoprotegerin). A163G, G209A, T245G and G1181C polymorphisms were determined. Results No significant differences in age, anthropometry, number of fractures, osteocalcin and cross-laps were found between women with and without osteoporosis. Women with osteoporosis were significantly longer in postmenopause. Significantly more women with osteoporosis had AG polymorphism (p = 0.038) compared to women without osteoporosis, while no significant difference was found in prevalence of TT and GG polymorphism between patients with and without osteoporosis. No relationship was found between investigated polymorphism and bone turnover markers. A significant negative correlation between total hip BMD and crosslaps (p = 0.046) as well as between total hip T score and crosslaps (p = 0.044) was found in women without osteoporosis Conclusions Postmenopausal women with osteoporosis had AG polymorphism more frequently than women without osteoporosis. Our results indicate that A163G polymorphism could have an impact on higher bone loss in postmenopausal women. PMID:27407270

C-reactive protein (CRP) is an important molecule in the defence against bacterial infections. To discover if variation in the CRP gene is associated with clinical outcome of bacteraemia, we investigated 147 microbiologically verified bacteraemia patients (mean age 59 y, range 19-93 y) and determined whether CRP -717A>G, +1059G>C or +1444C>T single nucleotide polymorphisms (SNPs) were associated with clinical outcome of bacteraemia and/or CRP concentration caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-haemolytic streptococci or Escherichia coli. The patients were genotyped for CRP genepolymorphisms, CRP was measured and clinical outcomes were recorded. The CRP -717A>G, a promoter region polymorphism was strongly associated with mortality from Streptococcus pneumoniae but did not correlate with plasma CRP concentration. These results suggest that mortality from Streptococcus pneumoniae may be associated with polymorphism of the promoter region of the CRP gene.

Full Text Available Background: Gastric cancer is one of the most common diseases of digestive system with a low 5-year survival rate and metastasis is the main cause of death. Multi-factors, such as changes in molecular pathways and deregulation of cells are involved in the disease development. Epidermal growth factor receptor pathway (EGFR which is associated with cell proliferation and survival can influence cancer development. EGFR function is governed by its genetic polymorphism; thus, we aimed to study the tyrosine kinase domain gene mutations of the receptor in patients with gastric cancer.Methods : In this experimental study, 123 subjects (83 patients with gastric cancer and 40 normal subjects were investigated in north of Iran for EGFR genepolymorphisms during 1 year. Genomic DNA was extracted by DNA extraction kit according to the manufacture's protocol. Polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP and silver staining were performed for investigating EGFR genepolymorphisms. Results : The participants included 72 men and 44 women. Genepolymorphism in exon 18 was present in 10% of the study population but SSCP pattern in exon 19 did not show different migrate bands neither in patients nor in normal subjects.Conclusion: It seems that screening for tyrosine kinas genepolymorphism of epidermal growth factor receptor in patients with gastric cancer and use of tyrosine kinas inhibitors could be useful in the prevention of disease progress and improvement of treatment process for a better quality of life in these patients.

Full Text Available Estrogen plays a role in the pathogenesis of leiomyoma. The CYP17 gene codes for the cytochrome P450c17alpha enzyme, which is involved in the biosynthesis of estrogen. Our aim was to investigate if CYP17 polymorphism could be a useful marker to predict the susceptibility to leiomyoma. Our sample of female subjects was divided into two groups: (1 with leiomyoma (n = 159; (2 without leiomyoma (n = 128. A 169-bp fragment encompassing the A1/A2 polymorphic site of the CYP17 gene was amplified by polymerase chain reaction (PCR, restricted by enzyme MspA1I and electrophored on agarose gel. Genotypes and allelic frequencies for this polymorphism in both groups were compared. There was no significant difference between the two groups regarding the distribution of the CYP17 genepolymorphism frequencies. The A1 homozygote/heterozygote/A2 homozygote proportions for CYP17 in both groups were: (1 17.0/46.5/36.5%, and (2 17.2/45.3/37.5%. The proportions for alleles A1 and A2 were also comparable in the two groups. A1 and A2 allele frequencies were: 7% (40.3/59 in group 1, and 2% (39.8/60 in group 2. No significant association was observed between the risk of leiomyoma and polymorphisms of the CYP 17 gene. So, CYP17 genepolymorphism does not appear to be a useful marker for the prediction of leiomyoma susceptibility.

Full Text Available Oxytocin is crucially involved in the onset and maintenance of labor. We investigated the association between oxytocin receptor genepolymorphisms and preterm birth. The presence of four common oxytocin receptor genepolymorphisms (rs2254298, rs53576, rs2228485 and rs237911 was evaluated in one hundred women with preterm birth and one hundred healthy women using restriction fragment length polymorphism genotyping. No association was found between the presence of any individual oxytocin receptor genepolymorphism and preterm birth. In haplotype analysis, the haplotype combination of rs2254298 A allele, rs2228485 C allele and rs237911 G allele was found to be significantly associated with an increased risk of preterm birth (OR = 3.2 [CI 1.04–9.8], p = 0.043. In conclusion our findings suggest that a combination of three oxytocin receptor genepolymorphisms is associated with an increased risk for preterm birth. We propose further studies investigating the role of oxytocin receptor genepolymorphisms and preterm birth.

The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes. We hypothesized that HS6ST3 genepolymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity $(P \\lt 0.05)$. SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples $(P = 0.0105)$. The T–A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample $(P = 0.012)$. Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample $(P \\lt 0.05)$ and the best signal was rs1927796 $(P = 0.00858)$. In addition, rs7331762 showed a strong gene × gender interaction $(P = 0.00956)$ for obesity while rs1927796 showed a strong gene × gender interaction $(P = 0.000625)$ for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

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Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR. The genotype frequencies were as follows: 6.6% for homozygous wild type, 41.8% for heterozygous and 51.6% for homozygous polymorphic genotype carriers of TAS1R2 gene rs35874116; 27.8% for heterozygous and 72.2% for homozygous polymorphic genotype carriers of TAS1R2 gene rs9701796, and 83.1% for homozygous wild type and 16.9% for heterozygous genotype carriers of TAS1R3 gene rs307355 polymorphism. A significant association was observed between total caries experience (dft + DMFT - decayed filled primary teeth + decayed, missing and filled permanent teeth) and TAS1R2 rs35874116 (p = 0.008) and TAS1R3 rs307355 (p = 0.04) genepolymorphisms but not for TAS1R2 gene rs9701796 polymorphism. TAS1R3 gene rs307355 polymorphism has been found to be an independent risk factor for dental caries experience by logistic regression analysis and to have increased the risk of caries. Moderate caries experience (4-7 caries) was found to be associated with TAS1R3 rs307355 heterozygous genotype, whereas high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype.

Full Text Available Introduction: Osteoporosis is a common age-related disease that is strongly influenced by genetics. Polymorphisms of the estrogen receptor gene alpha (ESR1 are consistently been associated with bone mineral density (BMD and fracture. The purpose of this investigation was to evaluate potential association of single nucleotide polymorphism (SNP variants of the ESR1 gene and bone mineral density (BMD of the lumbar spine in Kazakh women. Methods: 140 female participants in Pavlodar clinics with varying measures of BMD. We are examined the potential association of BMD with 2 SNPs from the ESR1 gene (rs2234693 [PvuII] and rs9340799 [XbaI]. Genotyping of the PvuII and XbaI polymorphisms was performed by direct sequencing of the gene fragments containing restriction sites with the identification of genotypes PP, Pp, pp and XX, Xx, xx respectively. Results: Unadjusted mean BMD values ranged from 1.14±0.14 g/cm2 in Caucasian women and 1.03±0.11 g/cm2 in Asian women. The association between PvuII polymorphism and BMD at the lumbar spine (p= 0.04 for PP=Pp=pp was statistically significant in all women. The XbaI polymorphism was not associated with BMD at lumbar spine. The relative risk for low BMD was higher for the marker PvuII (RR=1.51 than for the marker XbaI (RR=1.35. Conclusion: The PvuII polymorphism had a weak association with lumbar spine BMD. XbaI polymorphism was unlikely to be a predictor of lumbar spine BMD in Kazakh women. These conclusions could help to determine the genetic risk factors for osteoporosis; however, further studies on the association between genepolymorphisms and BMD are needed including larger numbers of participants and genes to clarify genetic risks.

Full Text Available Abstract Objective One of the important proteins involved in lipid metabolism is the ATP-binding cassette transporter A1 (ABCA1 encoding by ABCA1 gene. In this study we evaluated the single nucleotide polymorphisms (SNPs of ABCA1 gene. We analyzed SNPs in chromosome 9 such as rs2230806 (R219K in the position 107620867, rs2230808 (R1587K in the position 106602625 and rs4149313 (I883M in the position 106626574 according to gender and lipid profile of Greek nurses. Methods The study population consisted of 447 (87 men unrelated nurses who were genotyped for ABCA1 genepolymorphisms. Additionally, lipid profile [total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-C and apolipoprotein A1] was evaluated. Results The distribution of all three studied ABCA1 genepolymorphisms did not differ according to gender. However, only R219K genotype distribution bared borderline statistical significance (p = 0.08 between the two studied groups. Moreover, allele frequencies of R219K, R1587K and I88M polymorphisms did not differ according to gender. In general, blood lipid levels did not seem to vary according to ABCA1 genepolymorphisms, when testing all subjects or when testing only men or only women. However, a significant difference of LDL-C distribution was detected in all subjects according to R1587K genotype, indicating lower LDL-C levels with KK polymorphism (p = 0.0025. The above difference was solely detected on female population (p = 0.0053. Conclusions The ABCA1 genepolymorphisms frequency, distribution and lipid profile did not differ according to gender. However, in the female population the KK genotype of R1587K gene indicated lower LDL-C levels. Further studies, involving a higher number of individuals, are required to clarify genes and gender contribution.

Full Text Available In several DNA repair genes, polymorphisms may result in reduced repair capacity, which has been implicated as a risk factor for various types of cancer. The frequency of the polymorphic alleles varies among populations, suggesting an ethnic distribution of genotypes. We genotyped 300 healthy Southeastern Brazilian individuals (262 of European ancestry and 38 of African ancestry for polymorphisms of codons 194 and 399 of the XRCC1 base excision repair pathway gene and of codon 241 of the XRCC3 homologous recombination repair pathway gene. The allele frequencies were 0.07 for the Arg194Trp and 0.33 for the Arg399Gln codons of the XRCC1 gene and 0.35 for the Thr241Met codon of the XRCC3 gene. The genotypic frequencies were within Hardy-Weinberg equilibrium. These frequencies showed ethnic variability when compared with those obtained for different populations from several countries.

Full Text Available The renin-angiotensin-aldosterone system (RAAS plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS genepolymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D, angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms.A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy.The relationship between RAAS genepolymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. Conclusion: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis.Although a role of RAAS genepolymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

Full Text Available Background. Transporter associated with antigen processing (TAP is responsible for peptide loading onto class I major histocompatibility complex (MHC-I molecules. TAP seems to facilitate the detection of HPV by MHC-I molecules and contributes to successful eradication of HPV. TAP polymorphisms could have an important impact on the course of HPV infection. Objective. The aim of this study is to evaluate the association between five TAP genepolymorphisms and the risk of CIN. Methods. This case-control study investigated five common TAP polymorphisms in TAP1 (1341 and 2254 and TAP2 (1135, 1693, and 1993 in 616 women with CIN and 206 controls. Associations between genepolymorphisms and risk of CIN were analysed by univariate and multivariable models. The combined effect of the five TAP genepolymorphisms on the risk for CIN was investigated by haplotype analysis. Results. No significant difference in genotype distribution of the five TAP polymorphisms was observed in women with CIN and controls. Haplotype analysis revealed that women with haplotype mut-wt-wt-wt-wt (TAP polymorphisms t1135-t1341-t1693-t1993-t2254 had a significantly lower risk for CIN, compared to women with the haplotype wt-wt-wt-wt-wt (; OR 0.5 []. Conclusion. Identification of this haplotype combination could be used to identify women, less susceptible for development of CIN following HPV infection.

Full Text Available Abstract Background The risk of common diseases is likely determined by the complex interplay between environmental and genetic factors, including single nucleotide polymorphisms (SNPs. Traditional methods of data analysis are poorly suited for detecting complex interactions due to sparseness of data in high dimensions, which often occurs when data are available for a large number of SNPs for a relatively small number of samples. Validation of associations observed using multiple methods should be implemented to minimize likelihood of false-positive associations. Moreover, high-throughput genotyping methods allow investigators to genotype thousands of SNPs at one time. Investigating associations for each individual SNP or interactions between SNPs using traditional approaches is inefficient and prone to false positives. Results We developed the Polymorphism Interaction Analysis tool (PIA version 2.0 to include different approaches for ranking and scoring SNP combinations, to account for imbalances between case and control ratios, stratify on particular factors, and examine associations of user-defined pathways (based on SNP or gene with case status. PIA v. 2.0 detected 2-SNP interactions as the highest ranking model 77% of the time, using simulated data sets of genetic models of interaction (minor allele frequency = 0.2; heritability = 0.01; N = 1600 generated previously [Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH: A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol 2007, 31:306–315.]. Interacting SNPs were detected in both balanced (20 SNPs and imbalanced data (case:control 1:2 and 1:4, 10 SNPs in the context of non-interacting SNPs. Conclusion PIA v. 2.0 is a useful tool for exploring gene*gene or gene*environment interactions and identifying a small number of putative associations which may be investigated further using other

Full Text Available Background Type 2 Diabetes (T2D is a chronic metabolic disease associated with increased mortality and morbidity. High levels of glucose can damage organs, such as the kidneys, eyes and nerves. Oxytocin (OXT can regulate feeding behavior, energy balance, insulin sensitivity and insulin secretion. The OXT Receptor (OXTR mediates the action of OXT on cells. The role of OXTR polymorphism in carbohydrate metabolism disorders, especially in T2D, is not clear. Objectives The current study aimed to investigate the possible associations between OXTR polymorphism and the risk of developing T2D. Patients and Methods To study genetic polymorphisms, 120 patients with T2D and 120 controls were selected. Genotyping of the OXTR rs53576 and rs2254298 variants was performed using allele-specific Polymerase Chain Reaction (PCR and Restriction Fragment Length Polymorphism (RFLP PCR, respectively. Data were analyzed using Chi-square analysis and logistic regression. Results The logistic regression analysis suggested no significant associations of OXTR Single Nucleotide Polymorphism (SNP rs22542987 in genotypes (OR = 1.054, 95% CI: 0.557 - 1.995, P = 0.871 and alleles of patients with T2D in the study population (OR = 1.004, 95% CI: 0.547 - 1.845, P = 1. The rs53576 polymorphism showed the TT genotype (OR = 0.466, %95CI: 0.22 - 0.94, P = 0.035, as well as T allele (OR = 0.66, %95 CI: (0.46 - 0.95, P = 0.03 in the patients and control group with a significant difference suggesting the protective role this polymorphism plays in T2D. Conclusions Our findings showed that the genotype TT rs53576 OXTR, as well as T allele had significant differences in our population and play a protective role. Therefore, it is suggested to place more interest on these OXTR in large populations and different ethnic groups.

Recent attempts to discover genetic factors affecting cattle resistance/susceptibility to bovine spongiform encephalopathy (BSE) have led to the identification of two insertion/deletion (indel) polymorphisms, located within the promoter and intron 1 of the prion protein gene PRNP, showing a significant association with the occurrence of classical form of the disease. Because the effect of the polymorphisms was studied only in few populations, in this study we investigated whether previously described association of PRNP indel polymorphisms with BSE susceptibility in cattle is also present in Polish cattle population. We found a significant relation between the investigated PRNP indel polymorphisms (23 and 12 bp indels), and susceptibility of Polish Holstein-Friesian cattle to classical BSE (P polymorphisms were related to increased susceptibility, whereas insertion variants were protective against BSE.

Inflammatory genepolymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory genepolymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness. We recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory genepolymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP-1, ICAM-1, and TNF-α. Associations of CAVI with genetic and conventional risk factors were estimated by sex and age group (34-49, 50-59, and 60-69 years) using a general linear model. The association with 5-year change in CAVI was examined longitudinally. Glucose intolerance was associated with high CAVI among women in all age groups, while hypertension was associated with high CAVI among participants in all age groups, except younger women. Mean CAVI for the CD14 CC genotype was lower than those for the TT and CT genotypes (P for trend = 0.005), while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49 years (P = 0.006). No association of the other 6 polymorphisms with CAVI was observed. No association with 5-year change in CAVI was apparent. Inflammatory genepolymorphisms were not associated with arterial stiffness. To confirm these results, further large-scale prospective studies are warranted.

Full Text Available Background : The vitamin D receptor (VDR gene serves as a good candidate gene for susceptibility to several diseases. The gene has a critical role in regulating the renin-angiotensin system (RAS influencing the regulation of blood pressure. Hence determining the association of VDR polymorphisms with essential hypertension is expected to help in the evaluation of risk for the condition. Aim : The aim of this study was to evaluate association between VDR Fok I polymorphism and genetic susceptibility to essential hypertension. Materials and Methods : Two hundred and eighty clinically diagnosed hypertensive patients and 200 normotensive healthy controls were analyzed for Fok I (T/C [rs2228570] polymorphism by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP analysis. Genotype distribution and allele frequencies in patients and controls, and odds ratios (ORs were calculated to predict the risk for developing hypertension by the individuals of different genotypes. Results : The genotype distribution and allele frequencies of Fok I (T/C [rs2228570] VDR polymorphism differed significantly between patients and controls (χ2 of 18.0; 2 degrees of freedom; P = 0.000. FF genotype and allele F were at significantly greater risk for developing hypertension and the risk was elevated for both the sexes, cases with positive family history and habit of smoking. Conclusions : Our data suggest that VDR gene Fok I polymorphism is associated with the risk of developing essential hypertension

Full Text Available Epidemiological studies have suggested that interleukin-17 (IL-17 polymorphisms are associated with cancer risk. However, the results of these studies are inconsistent. Therefore, we performed a meta-analysis to obtain a precise conclusion. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the association of the IL-17A rs2275913G>A and IL-17F rs763780T>C polymorphisms with cancer risk. Publication bias and sensitivity analyses were performed to ensure the statistical power. Overall, 10 relevant case-control studies involving 4,516 cases and 5,645 controls were included. The pooled ORs with 95% CIs indicated that the IL-17A rs2275913G>A polymorphism was significantly associated with increased cancer risk (for A versus G: OR = 1.28, 95% CI: 1.16–1.41, PC polymorphism was also significantly associated with gastric cancer development. Overall, the present meta-analysis suggests that IL-17 polymorphisms increase the risk of developing cancer, particularly gastric cancer, in the Asian (and Chinese population.

Background The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population. Material/Methods In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with ...

AIM: To investigate the relationship between the polymorphism of class Ⅱ transactivator (CⅡTA) gene promoters and chronic hepatitis B (CHB).METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Promoters Ⅰ, Ⅲ and Ⅳ of gene were analyzed respectively with polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 65 patients with CHB, 26 patients with acute hepatitis B (AHB) and 85 normal controls.RESULTS: No abnormal migration was found in PCR-SSCP analysis of the three promoters in the three groups. Also,no sequential difference was observed at the three promoters among the CHB patients, AHB patients and normal controls.CONCLUSION: No polymorphism in promoters Ⅰ, Ⅲ and Ⅳ of CⅡTA gene exists in CHB patients, ABH patients and normal controls, suggesting that the promoter of CⅡTA gene might be a conserved domain.

Objective: To explore the relationship between polymorphism of α2-macroglobulin (A2M)gene and Parkinson's disease (PD)in Han Nationality in Shanghai. Methods:The distributions of A2M genepolymorphism (a Val1000Ile in exon24, V/I)were detected in 66 PD patients and 120 healthy controls using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Results:The I allelic frequency in A2M exon24 gene of PD patients (90.9 %) was significantly lower than that of the healthy controls(96.3%)(OR=0.39,P=0. 033),so was the I/I genotype(OR=0.32,P=0. 015),especially in the patients more than 60 years old (OR= 0.31 ,P= 0.04). Conclusion :The I allele in exon24 of A2M gene might inhibit the onset of PD in Han Nationality in Shanghai.

AIM: To elucidate the possible difference in two promoter polymorphisms of the transforming growth factor-β1 (TGF-β1) gene (-800G > A, -509C > T)between ulcerative colitis (UC) patients and normal subjects.METHODS: A total of 155 patients with established ulcerative colitis and 139 normal subjects were selected as controls. Two single nucleotide polymorphisms within the promoter region of TGF-β1 gene (-509C > T and -800G > A) were genotyped using PCR-RFLP.RESULTS: There was a statistically significant difference in genotype and allele frequency distributions between UC patients and controls for the -800G > A polymorphism of the TGF-β1 gene (P A of TGF-β1 gene promoter between Iranian patients with UC and normal subjects.

Full Text Available The genetic diversity of a single nucleotide polymorphism (SNP at the exon 20 (T945M of the leptin receptor gene (LEPR and of three short tandem repeats (STRs BM7225, BMS694, and BMS2145 linked to LEPR was investigated in three beef cattle herds (Brangus Ibagé, Charolais, and Aberdeen Angus. A cheap and effective new method to analyze the T945M polymorphism in cattle populations was developed and the possible role of these polymorphisms in reproduction and weight gain of postpartum cows was evaluated. High levels of genetic diversity were observed with the average heterozygosity of STRs ranging from 0.71 to 0.81. No significant association was detected between LEPR markers and reproductive parameters or daily weight gain. These negative results suggest that the LEPR genepolymorphisms, at least those herein described, do not influence postpartum cows production.

High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.

We analyzed the relationship between Mink-S27 genepolymorphism and children with cardiac insufficiency. From April 2013 to April 2015, we enrolled 73 cases of children with cardiac insufficiency for this study, and all 73 were placed in the observation group. 76 normal cases were selected for the control group. Restriction fragment length polymorphism (RFLP) was used to make polymorphism analysis of the Mink-S27. Our results showed no significant differences in Mink-S27 genotype and allele distribution in both observation and control groups (p>0.05). In lesion samples collected from children with cardiac insufficiency, we detected significant difference in AA, CC genotype frequency and allele frequency between the observation group and the control group (prelatively high. GNAS2 genepolymorphism was associated with the prevalence of cardiac insufficiency in children. And also the patients' condition was correlated to the frequency of different genotypes and alleles.

Currently it is not well known whether apolipoprotein E (ApoE) is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases (58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage), and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between ApoE genepolymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the ApoE genepolymorphism and cerebral hemorrhage.

Full Text Available Tacrolimus (FK-506 is a part of most immunosuppressive protocols after kidney transplantation because it significantly affects the survival of transplanted organs in post - transplantation period. FK-506 is characterized by a narrow therapeutic index and large interindividual variability in pharmacokinetics. Partly, these variations can be explained by 6986A>G polymorphism CYP3A5 gene. As a substrate for CYP3A5 isoenzyme, FK–506 has a different elimination rate amnog individuals, which is caused by CYP3A5 genepolymorphism. The primary objective of this study was to investigate the frequency of CYP3A5 genepolymorphism (6986A>G in kidney transplant patients and comparison with the healthy volunteers. The second objective of this study was to determine the influence of the investigated polymorphism on FK–506 dosage regimen one month after kidney transplantation.Pharmacogenetic retrospective study included 121 examinees - 60 patients with renal transplant and 60 healthy volunteers. Patients have routine determination of drug concentration at the Clinic of Nephrology, Clinical Center Niš, Serbia. PCR method (Ashavaid TF et al. was used to determine the polymorphism of CYP3A5 gene. Our study did not show statistically significant differences in allele (p=0.616 and genotype (p=0.602 frequencies between the studied polymorphism in renal transplant patients and healthy volunteers. A statistically significant difference was found between patients with different genotypes of CYP3A5 regarding dose (p=0.001, weight adjusted dose (p=0.005, and dose normalized level of FK–506 (p=0.039 one month after transplantation. Patients with kidney transplant and healthy subjects in Serbian population did not show difference in the frequency of alleles of CYP3A5 gene. CYP3A5 genepolymorphism affects the dose regimen of tacrolimus one month after kidney transplantation. Acta Medica Medianae 2013;52(1:33-38.

Full Text Available Increased expression of epithelial cell-derived neutrophil-activating peptide (ENA-78 has been reported in several immune and inflammatory conditions suggesting its role in inflammatory response. We have identified two single nucleotide polymorphisms in the promoter and exon 2 of the ENA-78 gene by scanning the full length gene using DHPLC DNA fragment analysis and DNA sequencing.

Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the associat

The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade ...

Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, gen

The extent of restriction fragment length polymorphism in genes for the arginine deiminase enzyme among 28 species of mycoplasmas was assessed by Southern blot analysis of DNA digested with EcoRI or TaqI nuclease probed with a 725-bp internal fragment of the arginine deiminase gene from Mycoplasma arginini. The results indicated unexpected heterogeneity among species of a single genus.

-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome and connexin 40 genepolymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

textabstractThe estrogen receptor alpha gene (ESR1) is known to be involved in metabolic pathways influencing growth. We have performed two population-based association studies using three common polymorphisms within this candidate gene to determine whether these are associated with variation in adu

Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, gen

Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic

Objective: To explore the relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), the central enzymes in folate metabolism that affects DNA methylation and synthesis, and the risk of Down syndrome in China. Methods: Genomic DNA was isolated from the peripheral lymphocytes of 64 mothers of children with Down syndrome and 70 age matched control subjects. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFR 677C→T, MTRR 66A→G and the relationship between these genotypes and the risk of Down syndrome was analyzed. Results: The results show that the MTHFR 677C→T polymorphism is more prevalent among mothers of children with Down syndrome than among control mothers, with an odds ratio of 3.78 (95% confidence interval (CI), 1.78～8.47). In addition, the homozygous MTRR 66A→G polymorphism was independently associated with a 5.2-fold increase in estimated risk (95% CI, 1.90～14.22). The combined presence of both polymorphisms was associated with a greater risk of Down syndrome than the presence of either alone, with an odds ratio of 6.0 (95% CI, 2.058～17.496).The two polymorphisms appear to act without a multiplicative interaction. Conclusion: MTHFR and MTRR gene mutation alleles are related to Down syndrome, and CT, TT and GG gene mutation types increase the risk of Down syndrome.

Genetic factors related to cancer have been extensively studied and several polymorphisms have been associated to breast cancer. The FGFR4, MTHFR, and HFE genes have been associated with neoplastic diseases development. The current report outlines the analysis of the polymorphisms G388A (FGFR4), C677T (MTHFR), C282Y, and H63D (HFE) in Brazilian breast cancer patients. We studied 68 patients with invasive ductal and operable breast carcinoma and 85 women as a control group. The polymorphism frequencies in the breast cancer and control groups were analyzed, but no significant difference was observed by comparing the two groups. The presence of each polymorphism was analyzed according to the clinical features and markers already established as prognostic in the breast cancer group. The C677T, H63D, and G388A polymorphisms were not associated to histological grade, age of diagnosis, expression of HER2 receptor, or estrogen and progesterone receptor. The H63D polymorphism showed a significant association (P = 0.02) with the presence of p53 mutations, and C667T showed association to lymph node involvement (P = 0.05). Lymph node involvement, G388A polymorphism, and histological grade were independently associated to metastasis/death. Our data suggests that the polymorphisms G388A, C677T, and H63D are not useful in breast cancer diagnosis, but they may be significant additional prognostic markers related to breast cancer survival.

Full Text Available The functional effect of the A>G transition at position 2756 on the MTR gene (5-methyltetrahydrofolate-homocysteine methyltransferase, involved in folate metabolism, may be a risk factor for head and neck squamous cell carcinoma (HNSCC. The frequency of MTR A2756G (rs1805087 polymorphism was compared between HNSCC patients and individuals without history of neoplasias. The association of this polymorphism with clinical histopathological parameters was evaluated. A total of 705 individuals were included in the study. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype the polymorphism. For statistical analysis, the chi-square test (univariate analysis was used for comparisons between groups and multiple logistic regression (multivariate analysis was used for interactions between the polymorphism and risk factors and clinical histopathological parameters. Using univariate analysis, the results did not show significant differences in allelic or genotypic distributions. Multivariable analysis showed that tobacco and alcohol consumption (P < 0.05, AG genotype (P = 0.019 and G allele (P = 0.028 may be predictors of the disease and a higher frequency of the G polymorphic allele was detected in men with HNSCC compared to male controls (P = 0.008. The analysis of polymorphism regarding clinical histopathological parameters did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion, our data provide evidence that supports an association between the polymorphism and the risk of HNSCC.

OBJECTIVE: To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness. DESIGN AND METHODS: The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and prevalence of overweight) are investigated in 582 participants of two large cohorts in The Netherlands (total 18 500 adult men and women), aged 20-40 years whose weight remained relatively constant or ...

Full Text Available Objective: Mutated p53 gene is related to the instability of cell growth and cell cycle progression. We aimed to evaluate the association between endometriosis and p53 codon 11, 72 and 248 genepolymorphisms. Patients and methods: Women were divided into two groups: (1 moderate/severe endometriosis (n=148, and (2 non-endometriosis groups (n=150. P53 genepolymorphisms include codon11 Glu/Gln or Lys (GAG->CAG or AAG, codon 72 Arg/Pro (CGC->CCC, and codon 248 Arg/Thr (CGG->TCG. These genepolymorphisms were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (Taq I, BstU I, Hap II digestions. Associations between the endometriosis and p53 polymorphisms were evaluated. Results: The distributions of p53 codon 72 polymorphisms in both groups were significantly different. The proportions of Arg homozygotes/heterozygotes/Pro homozygotes in both groups were 9.5/66.2/24.3% and 30.7/50/19.3%. The proportions of Arg/Pro alleles were 42.6/57.4% and 56/44%. The distributions of p53 codon 11 and 248 polymorphisms in both groups were non-significantly different. All individuals appeared the wild genotypes (Glu11 and Arg248 homozygotes. Conclusion: Association between endometriosis and p53 codon 72 polymorphism exists. P53 codon 72*Pro-related genotype and allele are related with higher susceptibility of endometriosis. P53 codon 11 and 248 polymorphisms are not related with endometriosis susceptibility.

A single-nucleotide polymorphism on the oxytocin receptor gene (OXTR), rs53576, involving a guanine (G) to adenine (A) substitution has been associated with altered prosocial features. Specifically, individuals with the GG genotype (i.e. the absence of the polymorphism) display beneficial traits including enhanced trust, empathy and self-esteem. However, because G carriers might also be more socially sensitive, this may render them more vulnerable to the adverse effects of a negative social s...

Objective To investigate the correlation between decoy receptor(DcR)1,DcR2 and osteoprotegerin(OPG)genepolymorphisms with the susceptibility to ulcerative colitis(UC)in Chinese population.Methods A total of352 patients with UC as well as 463 sex-and agematched healthy controls were recruited in the study.The genetic polymorphisms of DcR1(rs12549481),DcR2(rs1133782)and OPG(rs3102735)were deter-

Introduction: The production of cytokines, growth factors and adhesion molecules promotes tumor progression and involves inflammation, angiogenesis and thrombosis, thus providing optimal conditions for cancer development. Materials and methods: The present study was undertaken to evaluate association of cytokine genepolymorphisms with cervical cancer in a north Indian population. Genotyping of single nucleotide polymorphisms (SNPs) viz. IL-6-597G/A (rs1800797), IL-1β-511C/T (rs16944) and ...

We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism, affect maternal risk for Down syndrome. We investigated 76 Down syndrome mothers and 115 control mothers from Bengbu, China. Genomic DNA was isolated from the peripheral lymphocytes. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFD G1958A and TC C776G. The frequencies of the polymorphic alleles were 24.3 and 19.1% for MTHFD 1958A, 53.9 and 54.2% for TC 776G, in the case and control groups, respectively. No significant differences were found between two groups in relation to either the allele or the genotype frequency for both polymorphisms. However, when gene-gene interactions between these two polymorphisms together with previous studied C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were analyzed, the combined MTHFR 677CT/TT and MTHFD 1958AA/GA genotype was found to be significantly associated with the risk of having a Down syndrome child [odds ratio (OR) = 3.11; 95% confidence interval (95%CI) = 1.07-9.02]. In addition, the combined TC 776CG and MTHFR 677TT genotype increased the risk of having a child with Down syndrome 3.64-fold (OR = 3.64; 95%CI = 1.28-10.31). In conclusion, neither MTHFD G1958A nor TC C776G polymorphisms are an independent risk factor for Down syndrome. However, the combined MTHFD/MTHFR, TC/MTHFR genotypes play a role in the risk of bearing a Down syndrome child in the Chinese population.

OBJECTIVES: The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size...

Sequence polymorphisms within the 5'HS2 segment of human locus control region is described among sickle cell anemia patients. Distinct polymorphic patterns of a simple sequence repeat are observed in strong linkage disequilibrium with each of the five major beta s haplotypes. Potential functional relevance of this polymorphic region in globin gene expression is discussed.

Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC]{sub n} microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC]{sub n} microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873mSv. When the interaction between radiation dose and each DNA repair genepolymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele >=20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations.

Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 genepolymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 genepolymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 genepolymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.

Objective The objective of this study was to investigate whether there was a correlation between catechol-o-methyltransferase (COMT) genepolymorphism, which is believed to play a role in the etiology of psychotic disorders, and premenstrual syndrome (PMS). Methods Fifty-three women with regular menstrual cycles, aged between 18 and 46 years and diagnosed with PMS according to the American Congress of Obstetrics and Gynecology criteria were included in this study as the study group, and 53 healthy women having no health problems were selected as the controls. Venous blood was collected from all patients included in the study and kept at -18℃ prior to analysis. Results There was no significant difference between the groups in terms of demographic features such as age, body mass index, number of pregnancies, parity, and number of children. No statistically significant difference was observed in terms of COMT genepolymorphism (p=0.61) between women in the PMS and the control groups. However, a significant difference was found between arthralgia, which is an indicator of PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04). Conclusion These results suggested that there was no significant relationship between PMS and COMT genepolymorphism. Since we could not find a direct correlation between the COMT genepolymorphism and PMS, further studies including alternative neurotransmitter pathways are needed to find an effective treatment for this disease. PMID:25045629

Full Text Available The pathogenesis of essential hypertension (EH is affected by genetic and environmental factors. Mutations in hypertension-related genes can affect blood pressure (BP via alteration of salt and water reabsorption by the nephron. The genes of the renin-angiotensin system (RAS have been extensively studied because of the well documented role of this system in the control of BP. It has been previously shown that Angiotensin II type 1 receptor (ATR1 genepolymorphism could be associated with increased risk of EH. So, in the current study, we evaluated the frequency of ATR1 (A1166C polymorphism in relation to EH in a group of Egyptian population. The study population included 83 hypertensive patients and 60 age and sex matched healthy control subjects. Restriction fragment length polymorphism – Polymerase chain reaction (RFLP – PCR was used for the analysis of A1166C polymorphism of ATR1 genes in peripheral blood samples of all patients and controls. The results revealed that there was a positive risk of developing EH when having the T allele whether in homozygous or heterozygous state. From this work, it was concluded that there was an association between ATR1 (A1166C genepolymorphism and the risk of developing EH.

Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R genepolymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

Background: Recurrent pregnancy loss (RPL) is a multifactorial disorder. Environmental factors and genetics can affect pregnancy outcomes. Objective: Conflicting data suggest an association between estrogen receptor alpha (ESR1) genepolymorphisms and RPL. In this study, such association was investigated in Iranian women with RPL. Materials and Methods: In this case control study, blood samples were collected from 244 women with a history of three or more consecutive pregnancy losses and 104 healthy women with at least two live births. Using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control subjects. Results: The genotypic frequencies of -397C/T and -351A/G polymorphisms on ESR1were not significantly different between RPL and control groups (p=0.20 and p=0.09, respectively). A significantly negative correlation was observed between -397C/T and -351A/G (r=-0.852, p<0.001) in RPL women and complete linkage disequilibrium between the investigated polymorphisms was found (D’: 0.959; r-square= 0.758, p<0.001). Conclusion: This investigation suggests that the analyzed polymorphisms on ESR1gene are not associated with an increased risk of RPL in the studied population. PMID:25071847

The aim of this study was to examine the association between tHbmass and HBB genepolymorphisms in athletes of endurance disciplines. Eighty-two well-trained athletes (female n=36, male n=46), aged 19.3 ± 2.7 years, representing cross country skiing (n=37) and middle- and long-distance running (n=45), participated in the study. Genotyping for 2 polymorphisms in the HBB gene (- 551C/T and intron 2, +16 C/G) was performed using restriction fragment length polymorphism analysis. Total haemoglobin mass (tHbmass) was determined by the optimized carbon monoxide rebreathing method. Blood morphology, indices of iron status (ferritin, transferrin receptor and total iron binding capacity) and C reactive protein were also determined. No differences were found in the HBB genotype and allele frequencies between male and female athletes. Regardless of the polymorphisms, no relationships were found between HBB genotypes as well as alleles and relative values of tHbmass, expressed per body mass (g · kg(-1) BM), both in female and male athletes. Our results demonstrated that -551 C/T and intron 2, +16 C/G polymorphisms of the HBB gene have no association with total haemoglobin mass in endurance athletes. It cannot be ruled out that several polymorphisms, each with a small but significant contribution, may be responsible for the amount of haemoglobin.

Objective. To investigate whether the polymorphisms in the angiotensin converting enxyme (ACE) gene and angiotensinogen (AGT) gene are associated with essential hypertension. Methods. A case-contrul study was carried out using 103 hypertensive (HT) and 131 normotensive (NT) subjects. The insertion/daletion(I/D) polymorphism of the ACE gene and the methionine→threonine variant at position 235 (M235T) of the AGT gene were determined by the polymerase chain reaction (PCR) technique and PCR/restriction fragment length polymorphism (PCR/RFLP) analysis, respectively. Results. The differences of D allele frequency and genotype distribution of the ACE gene between NT and HT groups were statistically significant (X2= 18.12,P<0. 005). The T235 allele frequeacy of the AGT gene was 69% in NT Chinese group (approximately 1.38 to 1.64 fold that in Caucasians), and was greater in female HT than in NT (0.82 vs 0. 72, X2=8. 1,P<0.025). A corralation between M235T molecular variant of the AGT gene and I/D molecular variant of ACE gene to hypertension was found. Concluions. The possession of D allele of the ACE gene might be a marker for predisposition to hypertension. The T235 allele of the AGT gene was more common in Chinese than in Caucasians, and might contribute to the risk for hypertension in female Chinese.

Full Text Available Context: Asthma is a complex disease with multiple genetic and environmental factors contributing to it. A component of this complexity is a highly variable response to pharmacological therapy. Pharmacogenomics is the study of the role of genetic determinants in the variable response to therapy. A number of examples of possible pharmacogenomic approaches that may prove of value in the management of asthma are discussed below. Evidence Acquisition: A search of PubMed, Google scholar, E-Medicine, BMJ and Mbase was done using the key words "pharmacogenomics of asthma", "pharmacogenomics of β-agonist, glucocorticoids, leukotriene modifiers, theophylline, muscarinic antagonists in asthma". Results: Presently, there are limited examples of genepolymorphism that can influence response to asthma therapy. Polymorphisms that alter response to asthma therapy include Arg16Gly, Gln27Glu, Thr164Ile for β-agonist receptor, polymorphism of glucocorticoid receptor gene, CRHR1 variants and polymorphism of LTC4S, ALOX5. Polymorphic variants of muscarinic receptors, PDE4 and CYP450 gene variants. Conclusion: It was concluded that genetic variation can improve the response to asthma therapy. However, no genepolymorphism has been associated with consistent results in different populations. Therefore, asthma pharmacogenomic studies in different populations with a large number of subjects are required to make possible tailoring the asthma therapy according to the genetic characteristic of individual patient.

Peptidase S (PEPS) is a metallopeptidase that cleaves N-terminal residues from proteins and peptides. PEPS is used as a cell maintenance enzyme with critical roles in peptide turnover. The promoter region located upstream of the initiation site plays an important role in regulating gene expression. Polymorphism in the promoter region can alter gene expression and lead to biological changes. In the current study, polymorphisms in the promoter region of the PEPS gene were investigated. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and DNA sequencing methods were used to screen sequence variations in the promoter region of DNA samples from 743 Chinese Holstein cattle. Two polymorphisms (g. -534 T>C and g. -2545 G>A) were identified and eight haplotypes were classified by haplotype analysis. The two genetic polymorphisms and haplotypes were associated with fat percentage and somatic cell score in Chinese Holstein cattle. The results of real-time PCR showed that cow kidneys exhibit the highest PEPS expression level. Moreover, bioinformatics analysis predicted that the single-nucleotide polymorphism g. -534 T>C is located in the core promoter region and in the transcription factor binding sites. The promoter activities of the polymorphism of -543 T>C were measured by luciferase assay in the human kidney epithelial cell line 293T. Transcriptional activity is significantly lower in cell lines transfected with the reporter construct containing 2.5 kb upstream fragments with -543 C than in those with wild-type -543 T. The results indicated that genetic variation at locus -543 influences PEPS promoter activity. The genetic variation in the promoter region of PEPS gene may regulate PEPS gene transcription and might have consequences at a regulatory level.

Genepolymorphisms shared between recently diverged species are thought to be widespread and most commonly reflect introgression from hybridization or retention of ancestral polymorphism through incomplete lineage sorting. Shared genetic diversity resulting from incomplete lineage sorting is usually maintained for a relatively short period of time, but under strong balancing selection it may persist for millions of years beyond species divergence (balanced trans-species polymorphism), as in the case of the major histocompatibility complex (MHC) genes. However, balancing selection is much less likely to act on non-MHC immune genes. The aim of this study was to investigate the patterns of shared polymorphism and selection at non-MHC immune genes in five grouse species from Centrocercus and Tympanuchus genera. For this purpose, we genotyped five non-MHC immune genes that do not interact directly with pathogens, but are involved in signaling and regulate immune cell growth. In contrast to previous studies with MHC, we found no evidence for balancing selection or balanced trans-species polymorphism among the non-MHC immune genes. No haplotypes were shared between genera and in most cases more similar allelic variants sorted by genus. Between species within genera, however, we found extensive shared polymorphism, which was most likely attributable to introgression or incomplete lineage sorting following recent divergence and large ancestral effective population size (i.e., weak genetic drift). Our study suggests that North American prairie grouse may have attained relatively low degree of reciprocal monophyly at nuclear loci and reinforces the rarity of balancing selection in non-MHC immune genes.

Full Text Available Some studies have reported that angiotensin converting enzyme (ACE and angiotensinogen (AGT genes have been associated with hypertrophic cardiomyopathy (HCM. However, there have been inconsonant results among different studies. To clarify the influence of ACE and AGT on HCM, a systemic review and meta-analysis of case-control studies were performed. The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included "hypertrophic cardiomyopathy", "angiotensin converting enzyme" (ACE or "ACE" and "polymorphism or mutation". For the association of AGT M235T polymorphism and HCM, "angiotensin converting enzyme" or "ACE" was replaced with "angiotensinogen". A total of seventeen studies were included in our review. For the association of ACE I/D polymorphism and HCM, eleven literatures were included in the meta-analysis on association of penetrance and genotype. Similarly, six case-control studies were included in the meta-analysis for AGT M235T. For ACE I/D polymorphism, the comparison of DI/II genotype vs DD genotype was performed in the present meta-analysis. The OR was 0.73 (95% CI: 0.527, 0.998, P = 0.049, power = 94%, alpha = 0.05 after the study which deviated from Hardy-Weinberg Equilibrium was excluded, indicating that the ACE I/D genepolymorphism might be associated with HCM. The AGT M235T polymorphism did not significantly affect the risk of HCM. In addition, ACE I/D genepolymorphism did not significantly influence the interventricular septal thickness in HCM patients. In conclusion, the ACE I/D polymorphism might be associated with the risk of HCM.

Full Text Available OBJECTIVES: Conflicting data from studies on the potential role of multidrug resistance 1 genepolymorphisms in inflammatory bowel disease may result from the analysis of genetically and geographically distinct populations. Here, we investigated whether multidrug resistance 1 genepolymorphisms are associated with inflammatory bowel diseases in patients from Rio de Janeiro. METHODS: We analyzed 123 Crohn's disease patients and 83 ulcerative colitis patients to determine the presence of the multidrug resistance 1 genepolymorphisms C1236T, G2677T and C3435T. In particular, the genotype frequencies of Crohn's disease and ulcerative colitis patients were analyzed. Genotype-phenotype associations with major clinical characteristics were established, and estimated risks were calculated for the mutations. RESULTS: No significant difference was observed in the genotype frequencies of the multidrug resistance 1 G2677T/A and C3435T polymorphisms between Crohn's disease and ulcerative colitis patients. In contrast, the C1236T polymorphism was significantly more common in Crohn's disease than in ulcerative colitis (p = 0.047. A significant association was also found between the multidrug resistance 1 C3435T polymorphism and the stricturing form of Crohn's disease (OR: 4.13; p = 0.009, whereas no association was found with penetrating behavior (OR: 0.33; p = 0.094. In Crohn's disease, a positive association was also found between the C3435T polymorphism and corticosteroid resistance/refractoriness (OR: 4.14; p = 0.010. However, no significant association was found between multidrug resistance 1 genepolymorphisms and UC subphenotypic categories. CONCLUSION: The multidrug resistance 1 genepolymorphism C3435T is associated with the stricturing phenotype and an inappropriate response to therapy in Crohn's disease. This association with Crohn's disease may support additional pathogenic roles for the multidrug resistance 1 gene in regulating gut

for exon 2 of DQB using capillary electrophoresis single-strand conformation polymorphism, cloning, and sequencing. We found 21 different alleles. Four individuals show three alleles implying a duplication event in the history of this gene. Each distinct sequence translates to give a distinct amino acid......In order to test if DQB is a good candidate marker to investigate the relationship between major histocompatibility complex genes and pathogens in natural populations of Mastomys natalensis, we assessed the polymorphism and evolutionary history of this gene. Twenty-four individuals were genotyped...... sequence and there are strong signals of positive selection on peptide binding sites. Signals of recombination were found in the sequences suggesting that recombination has played a role in generating allelic diversity. Although trans-taxon polymorphism is present at the interspecific level in DQB exon 2...

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin genepolymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin genepolymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

Introduction Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias. Material and methods Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP). Results Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models. Conclusions The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias. PMID:26251756

Full Text Available OBJECTIVE: The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women. METHODS: A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction. RESULTS: No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype. CONCLUSION: No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 genepolymorphisms was observed.

Th2-mediated immunity is critical for human defence against schistosome, and susceptibility to infection is controlled by a major genetic locus, mapped on the 5q31-q33 region comprising the genes IL4, IL5 and IL13. We have reported an association between the rs1800925 polymorphism in the IL13 promoter and infection levels in a Dogon population (693 subjects in Ségué and 148 in Boul), where Schistosoma haematobium is endemic. In the same population, we investigated whether other polymorphisms in genes involved in type 2 cytokine immune response could affect susceptibility to schistosome infection. By logistic regression analysis, we found an association between a single-nucleotide polymorphism (SNP) in the STAT6 gene (rs324013) and infection levels (P=0.04). We confirmed this association in analyses restricted to subjects under 20 years age and living in Boul, the village with the highest levels of infection (P=0.005). We detected an additive effect of the rs324013 and rs1800925 polymorphisms (P=0.011). These SNPs were not strongly correlated with any other tested markers surrounding the two genes. Furthermore, electrophoretic mobility shift assay has shown that both polymorphisms affect transcription factor binding. These results are consistent with the Th2 cytokine pathway enhancing resistance to schistosome infection in humans.

Full Text Available Abstract Backgroud Interleukin-10(IL-10 is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population. Methods We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP. Results There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN involvement (P = 0.041 and larger tumor size (P = 0.039 at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022 and higher tumor stage(p = 0.028 of breast cancer at the time of diagnosis compared with others. Conclusions Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.

Full Text Available Abstract Background Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. Methods Candidate single nucleotide polymorphisms (SNPs in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. Results None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. Conclusion Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity.

The pathogenesis of PCOS has not been definitively determined and includes a number of genes linked with steroidogenesis, regulation of gonadotropin secretion, actions of insulin, obesity as well as chronic inflammatory processes. Some authors indicate that PPARgamma play a role in insulin sensitivity and are probably involved in hyperandrogenism in PCOS. The aim of the study was to assess the frequency of the Pro12Ala and Pro115Gln PPARgamma2 genepolymorphisms in women with PCOS. 54 PCOS women and 51 healthy women were recruited. Genetic studies to detect Pro12Ala and Pro115Gln PPARgamma2 genepolymorphism were performed. In the whole studied group the Pro115Gln polymorphism of the PPARgamma2 gene was not found. The frequency of the Pro12Ala polymorphism was estimated at 26.47% in the controls and at 23.15% in the PCOS patients. Women from the control and PCOS groups with BMI > or = 30 had statistically higher occurrence of the Ala allele than women with BMI Pro12Ala polymorphism observed in the sample of women from the Lower Silesian population was significantly higher than in the majority of European populations.

The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies have found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.

Full Text Available Growth hormone (GH is an anabolic hormone which sintesized and secreted by somatrotop cell inpituitary anterior lobe. GH exert its effect on growth and metabolism by interacting with a specificreceptor on the surface of the target cells. Growth hormone receptor (GHR has been suggested ascandidate gene for traits related to meat production in Bovidae. The objectives of this study were toidentify polymorphism of GH and GHR genes in buffalo. The 452 DNA samples buffalo were collectedfrom five populations in Indonesia (Siborong-Borong-Medan (65, Lebak-Banten (29, Pandeglang-Banten (180, Semarang-Central Java, and Mataram-West Nusa Tenggara (103. A gene fragment of theGH|AluI gene at 432 bp located on exon 3 and GHR|AluI gene at 298 bp on exon 10 were successfullyamplified by using the techniques of a PCR (polymerase chain reaction and genotyped by PCR-RFLP(restriction fragment length polymorphism then -SSCP (single strand conformation polymorphism. Theresults showed no polymorphisms were detected in these genes. All buffaloes tested had LL genotype forlocus GH|AluI and AA genotype for locus GHR|AluI.

BACKGROUND: Autoimmune hepatitis is a chronic, generally progressive inflammatory disorder of the liver, of which the cause is unclear. It was demonstrated that genetic factors are involved in its pathogenesis. Previous studies showed that human leukocyte antigen in the major histocompatibility complex (MHC) is associated with susceptibility to autoimmune hepatitis. Current genome scanning studies suggest that genes outside the MHC also play a critical role in autoimmune disorders. This article focuses on our current understanding of the polymorphisms of these genes and their roles in the pathogenesis of autoimmune hepatitis. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords autoimmune hepatitis, polymorphism, CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR up to May 2011. Additional papers were identified by a manual search of the references from key articles. RESULTS: According to the case-control studies on genetic polymorphisms, at least six genes (CTLA-4, Fas, TNF-α, TGF-β1, TBX21 and VDR) are involved in autoimmune hepatitis besides HLA. So far, there has been no agreement about gene susceptibility and the actual clinical significance of these genes is still controversial. CONCLUSION: Studies on genepolymorphisms outside the MHC and knowledge of genetic predispositions for autoimmune hepatitis may not only elucidate pathogenic mechanisms, but also provide new targets for therapy in the future.

Full Text Available The etiology of respiratory distress syndrome (RDS is multifactorial and multigenic. Studies have suggested that polymorphisms and mutations in the surfactant protein B (SP-B gene are associated with the pathogenesis of RDS. The objectives of this study were to determine and compare the frequencies of SP-B genepolymorphisms in preterm babies with and without RDS. We studied 151 neonates: 79 preterm babies without RDS and 72 preterm newborns with RDS. The following four SP-B genepolymorphisms were analyzed: A/C at -18, C/T at 1580, A/G at 9306, and G/C at nucleotide 8714. The polymorphisms were detected by PCR amplification of genomic DNA and genotyping. The genotypes were determined using PCR-based converted restriction fragment length polymorphisms. The control group consisted of 42 (53% girls and 37 (47% boys. Weight ranged from 1170 to 3260 g and mean gestational age (GA was 33.9 weeks (range: 29 to 35 weeks and 6 days. The RDS group consisted of 31 (43% girls and 41 (57% boys. Weight ranged from 614 to 2410 g and mean GA was 32 weeks (range: 26 to 35 weeks. The logistic regression model showed that GA was the variable that most contributed to the occurrence of RDS. The AG genotype of the A/G polymorphism at position 9306 of the SP-B gene was a protective factor in this population (OR = 0.1681; 95%CI = 0.0426-0.6629. We did not detect differences in the frequencies of the other polymorphisms between the two groups of newborns.

Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.

Full Text Available Aim: An attempt has been made to study the toll-like receptors 4 (TLR4 genepolymorphism from cattle DNA to correlate with mastitis cows. Materials and Methods: In present investigation, two fragments of TLR4 gene named T4CRBR1 and T4CRBR2 of a 316 bp and 382 bp were amplified by polymerase chain reaction (PCR, respectively from Kankrej (22 and Triple cross (24 cattle. The genetic polymorphisms in the two populations were detected by a single-strand conformational polymorphism in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results: Results showed that both alleles (A and B of two loci were found in all the two populations and the value of polymorphism information content indicated that these were highly polymorphic. Statistical results of χ2 test indicated that two polymorphism sites in the two populations fit with Hardy–Weinberg equilibrium (p˂0.05. Meanwhile, the effect of polymorphism of TLR4 gene on the somatic cell score (SCS indicated the cattle with allele a in T4CRBR1 showed lower SCS than that of allele B (p<0.05. Thus, the allele A might play an important role in mastitis resistance in cows. Conclusion: The relationship between the bovine mastitis trait and the polymorphism of TLR4 gene indicated that the bovine TLR4 gene may play an important role in mastitis resistance.

To evaluate the association of intron 1 and exon 1 polymorphisms in the estrogen receptor alpha gene (ER-alpha) with endometriosis in women. Association study. Endometriosis Unit, Federal University of São Paulo. The control group consisted of volunteers older than 45 years who had no evidence of endometriosis antecedents. Two groups with the disease were evaluated: the first group had stage I or II endometriosis and the second group stage III or IV. Polymerase chain reaction (PCR) followed by digestion with HaeIII and MspI endonucleases (RFLP) were applied to detect intron 1 and exon 1 polymorphisms, respectively, in a total of 125 controls and 105 affected women. Frequency and distribution of HaeIII and MspI polymorphisms in ER-alpha. No significant differences in the frequency of polymorphisms either in intron 1 or exon 1 of ER-alpha were found when endometriosis patients were compared with control subjects. Furthermore, the frequency of ER-alpha polymorphisms within the two different groups of patients with disease was statistically similar. The odds ratio between presence of intron 1 single-nucleotide polymorphisms (SNP) and endometriosis was 0.904, and the odds ratio between exon 1 SNP and endometriosis was 0.976. The evaluated polymorphisms were not associated with endometriosis.

Genetic variations such as single nucleotide polymorphisms (SNPs) in prion protein coding gene, Prnp, greatly affect susceptibility to prion diseases in mammals. Here, the coding region of Prnp was screened for polymorphisms in redeared turtle, Trachemys scripta. Four polymorphisms, L203V, N205I, V225A and M237V, were common in 15 out of 30 turtles; in one sample, three SNPs, L203V, N205I and M237V, and in the remaining 14 samples, only L203V and N205I polymorphisms, were investigated. Besides, C658T, C664T, C670A and C823A SNPs were silent mutations. To elucidate the relationship between the SNPs and apoptosis, TUNEL assays and active caspase-3 immunodetection techniques in brain sections of the polymorphic samples were performed. The results revealed that TUNEL-positive cells and active caspase-3-positive cells in the turtles with four polymorphisms were significantly increased compared with those of the turtles with two polymorphisms (P<0.01 and P<0.05, respectively). In conclusion, this study provides preliminary information about the possible relationship between SNPs within the Prnp locus and apoptosis in a non-mammalian species, Trachemys scripta, in which prion disease has never been reported.

Full Text Available Abstract Background Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA. We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA. Methods Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed. Results The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity. Conclusions We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.

-rays. RESULTS: The rare allele of a splice site polymorphism, 151 + 1: G-T, was associated with increased fracture risk and reduced BMD in women. Two other loss-of-function polymorphisms, Glu496Ala and Gly150Arg, were also associated with BMD. The Glu496Ala variant allele was associated with decreased lumbar......UNLABELLED: The P2X(7) receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X(7) receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three...... of these polymorphisms were associated with BMD and fracture risk. INTRODUCTION: The P2X(7) receptor is an ATP-gated cation channel. P2X(7) receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X(7) receptor gene, we wanted...

AIM: To investigate TNF-α-308 and TNFB polymorphisms in acute biliary pancreatitis (ABP) and to related them to the plasma TNF-α levels.METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients (n=127) and healthy controls (n=-102)using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Reading the size of digested bands from polyacrylamide gel demonstrated the two alleles TNF1 and TNF2, or the two alleles TNFB1and TNFB2.RESULTS: The frequencies of TNF2 polymorphism and TNFB2 polymorphism were both similar in patients with mild or severe pancreatitis, so were in pancreatitis patients and in controls. Patients with septic shock showed a significantly higher prevalence of the TNF2 than those without. No significant differences were found in the genotype distribution of TNF-α-308 and TNFB among different groups. Plasma TNF-α levels did not differ significantly in ASBP patients displaying different alleles of the TNF gene studied.CONCLUSION: Results indicate that TNF genepolymorphisms studied play no part in determination of disease severity or susceptibility to acute biliary pancreatitis; however, TNF2polymorphism is associated with septic shock from ASBP.Genetic factors are not important in determining plasma TNF-α levels in ASBP.

Full Text Available Abstract Background Attention deficit hyperactivity disorder (ADHD is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/SLC6A3 has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD. Methods To investigate the association between the polymorphisms -67A/T (rs2975226 and -839C/T (rs2652511 in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197 and Taiwan (n = 212 were genotyped, and analysed using within-family transmission disequilibrium test (TDT. Results A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (P = 0.001. There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (P = 0.003. No association was detected between the -839C/T polymorphism and ADHD in either of the two populations. Conclusion The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.

Aim: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC genepolymorphisms on PCa risk by using a meta-analysis. Methods: Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. Results: A total of five separate case–control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/−polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/−polymorphism with PCa (p0.05). Conclusion: These analyses suggest that XPC gene PAT+/−polymorphism, but not rs2228001, likely contributes to susceptibility to PCa. PMID:24093803

Accumulated evidence suggests that the growth hormone (GH) gene plays a physiological role in the control of reproductive function. Here, we examined the correlation between egg-laying traits and GH genepolymorphisms and expression patterns in the muscovy duck (Cairina moschata). PCR single-strand conformation polymorphism was used to identify polymorphisms in intron 3 of GH. One single nucleotide polymorphism (g.3270 A > G) was detected by sequencing, and the frequencies of the A and G alleles in the population were 0.65 and 0.35, respectively. A comparison test showed that the AA genotype group had more consecutive laying days and more eggs at 300 days than the GG genotype group (P 0.05). Such a significant correlation between GH polymorphisms and egg-laying performance suggested that GH could be a candidate locus affecting the laying trait in muscovy duck. Furthermore, real-time fluorescent quantitative PCR demonstrated that GH is expressed in all selected tissues, but is highly expressed in the hypothalamic-pituitary-gonadal axis and heart. This unique expression pattern suggested that GH may exert its local physiological function through the autocrine or paracrine pathway during gonad development and growth in the muscovy duck. The data presented in this paper revealed GH polymorphisms and expression patterns in the muscovy duck and indicated a potential regulatory effect of GH on reproduction.

Full Text Available Interaction of prion protein and amyloid-b oligomers has been demonstrated recently. Homozygosity at prion protein gene (PRNP codon 129 is associated with higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed as a possible risk factor in Alzheimer disease (AD. Objective To describe the association between codon 129 polymorphisms and AD. Methods We investigated the association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls, and the association between this polymorphism and cognitive performance. Other polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE were evaluated. Results Codon 129 genotype distribution in AD 45.5% methionine (MM, 42.2% methionine valine (MV, 12.1% valine (VV; and 39.6% MM, 50.5% MV, 9.9% VV among controls (p>0.05. There were no differences of cognitive performance concerning codon 129. Stratification according to ApoE genotype did not reveal difference between groups. Conclusion Codon 129 polymorphism is not a risk factor for AD in Brazilian patients.

An extensive association analysis of PON gene cluster (PONs) with coronary heart disease (CHD) was performed in Chinese Han population. Eleven polymorphisms of PON1, PON2 and PON3 gene were investigated for association with CHD in 474 male patients and 475 controls. Univariate analyses showed the cases had significantly higher frequencies of PON1 192Q allele, 160R allele, -162A allele and PON2 311C allele than were seen in the controls. Logistic regression analyses revealed only the PON1 R160G and -162G/A polymorphisms remained significantly associated with CHD (P = 0.0054 and P = 0.0002). Haplotype analyses for various polymorphism combinations further confirmed the results of individual polymorphism analyses. Only the frequencies of haplotypes containing -162A allele were significantly higher,whereas only the frequencies of haplotypes containing 160G allele significantly lower in cases than those in controls in various polymorphism combinations. This extensive association study has identified the PON1 -162G/A and R160G polymorphisms to be independently associated with CHD in Chinese Han population,and warrants further study to elucidate the biological mechanism.

BACKGROUND: It is of significance for single nucleotide polymorphisms (SNPs),a difference of rank, which exists widely in biology, genetics and other fields.OBJECTIVE: To detect polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province.DESIGN: Simple random sampling.SETTING: Department of Surgery of the 118 Hospital of Chinese PLA.PARTICIPANTS: A total of 80 healthy people in Han nationality were selected from hospitals in Zhejiang province from August 2005 to January 2006. There were 43 males and 37 females aged from 3 to 78 years with the mean age of 39.5 years, and all subjects were consent. DNA which was used in genetic analysis was selected from peripheral venous blood of all subjects and maintained at -20 ℃.METHODS: Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene were detected with directly DNA sequencing technique.MAIN OUTCOME MEASURES: Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province.RESULTS: A total of 80 samples were involved in the final analysis. SNPs sites were found at the 119th base of exon-4 of p53 gene (the 72nd codon of p53 gene), the 670th base of upper start codon in promotor of Fas gene (Fas-670), and the 995th base of intron-7 of Fas gene, especially SNPs in the 995th base of intron-7 pf Fas gene, I.e. C→A transversion, was a new site.CONCLUSION: One unknown SNPs site is discovered in intron-7 of Fas gene of people in Han nationality in Zhejiang province. This study also proves that the 72nd codon exists in p53 gene and the -670 polymorphism site exists in promotor of Fas gene.

In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic...... situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture...

Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical and pathophy......Paraoxonases may exert anti-atherogenic action by reducing lipid peroxidation. Previous studies examined associations between polymorphisms in the paraoxonase 1 (PON1) gene and development of coronary artery disease (CAD), with inconsistent results. Given the similarities in clinical...... and pathophysiological risk factors of CAD and calcific aortic valve stenosis (CAVS), we postulated a link between PON1 alleles and CAVS progression....

HSP70 genes have been considered as promising schizophrenia candidate genes based on their protective role in the central nervous system under stress conditions. In this study, we analyzed the potential implication of HSPA1A +190G/C, HSPA1B +1267A/G, and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoid schizophrenia in a homogenous Caucasian Polish population. In addition, we investigated the association of the polymorphisms with the clinical variables of the disease. Two hundr...

Full Text Available The deleted in colorectal carcinoma (DCC gene is a potential tumor- suppressor gene on chromosome 18821.3. The relatively high frequency of loss of heterozygosity (LOH and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg to GGA (Gly at codon 201 resulting in three types of polymorphism: codon 201Gly type, codon 201Arg/Gly type, and codon 201Arg type. The codon 201Gly type occurred more frequently in disseminated (stages IV and IVs neuroblastomas (72% than in localized (stages I, II, and III tumors (48% (P=.035, and normal controls (38% (P=.024. In addition, the codon 201Gly type was significantly more common in tumors found clinically (65% than in those found by mass screening (35% (P=.002. The results suggested that the codon 201Gly type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

We utilized a heteroduplex method to screen for small mutations in Duchenne muscular dystrophy patients who did not have deletions or duplications. A dystrophin exon 53 heteroduplex band was identified in 14.4% of the affected patients. Direct sequencing of the amplified product from DNA producing the heteroduplex revealed the presence of a polymorphism in the coding region. The codon for asparagine was converted from AAT to AAC.

Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association....

The worldwide declines in amphibian populations have largely been caused by infectious fungi and bacteria. Given that vertebrate immunity against these extracellular pathogens is primarily functioned by the major histocompatibility complex (MHC) class II molecules, the characterization and the evolution of amphibian MHC class II genes have attracted increasing attention. The polymorphism of MHC class II genes was found to be correlated with susceptibility to fungal pathogens in many amphibian species, suggesting the importance of studies on MHC class II genes for amphibians. However, such studies on MHC class II gene evolution have rarely been conducted on amphibians in China. In this study, we chose Omei treefrog (Rhacophorus omeimontis), which lived moist environments easy for breeding bacteria, to study the polymorphism of its MHC class II genes and the underlying evolutionary mechanisms. We amplified the entire MHC class IIB exon 2 sequence in the R. omeimontis using newly designed primers. We detected 102 putative alleles in 146 individuals. The number of alleles per individual ranged from one to seven, indicating that there are at least four loci containing MHC class IIB genes in R. omeimontis. The allelic polymorphism estimated from the 102 alleles in R. omeimontis was not high compared to that estimated in other anuran species. No significant gene recombination was detected in the 102 MHC class IIB exon 2 sequences. In contrast, both gene duplication and balancing selection greatly contributed to the variability in MHC class IIB exon 2 sequences of R. omeimontis. This study lays the groundwork for the future researches to comprehensively analyze the evolution of amphibian MHC genes and to assess the role of MHC genepolymorphisms in resistance against extracellular pathogens for amphibians in China.

Catechol-O-Methyltransferase (COMT) is a critical regulator of catecholamine levels in the brain. A functional polymorphism of the COMT gene, val158met, has been linked to internalizing symptoms (i.e., depression and anxiety) in adolescents and adults. We extended this research by investigating whether the val158met polymorphism was associated with childhood symptoms of depression and anxiety in two independent samples of young children (Ns = 476 and 409). In both samples, preschool-aged children were genotyped for the COMT val158met polymorphism. Symptoms of psychopathology were assessed via parent interviews and primary caregiver reports. In both samples, children homozygous for the val allele had higher levels of depressive symptoms compared to children with at least one copy of the met allele. Our findings extend previous research in older participants by showing links between the COMT val158met polymorphism and internalizing symptoms in early childhood. PMID:23475824

Persistent wheeze in childhood is associated with airway inflammation. The present study investigated relationships between polymorphisms in inflammatory genes, exposure to tobacco smoke and furred pets and risk of recurrent wheeze in children. Within a birth cohort of 101,042 children we...... on number of episodes with wheeze (18 months), exposure to tobacco smoke and pet-keeping. Recurrent wheeze was defined as at least four episodes of wheeze before the child was 18 months old. There was a statistically significant association between the IL-13 Arg144Gln polymorphism and risk of recurrent...... wheeze (p = 0.01). Furthermore, there was a statistically significant interaction between this polymorphism and exposure to tobacco smoke during pregnancy, though this was probably a chance finding. There were no other statistically significant effects of the polymorphisms or interactions with exposure...

Full Text Available Bronchial asthma is a poligenic disorder caused by the influence of genetic and envioromental factors. The functional single nucleotide polymorphism (SNPs in the regulatory regions of the cytokine genes may affect the cytokine production and thus play a contributory role in the pathogenesis of asthma. Substitution of cytosine (C by thymine (T at the position -509 in the promoter region of the transforming growth factor β1 (TGF-β1 gene could be associated with asthma. The aim of this study was to investigate the association of the TGF-β1 C-509T polymorphism with asthma and to determine the distribution of this polymorphism in the Serbian population. A total of 57 patients with diagnosed asthma and 49 healthy controls were screened for TGF-β1 C-509T polymorphisms using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP method. The TGF-β1 C-509T genotype (p=0.413 and allele frequencies (p=0.227 distributions in patients did not reveal statistically significant difference compared to controls. Additionally, no difference in genotype and allele frequencies distribution between male and female subjects was observed. In conclusion, to the best knowledge of the authors, this is the first study examining the association of TGF-β1 C-509T polymorphism in the Serbian patients with asthma. The present study did not confirm the specific role of TGF-β1 C-509T polymorphisms in asthma. No differences in the distribution of TGF-β1 C-509T polymorphism between patients and healthy subjects were observed.

Full Text Available Abstract Objective As chronic obstructive pulmonary disease (COPD is known for poor glucocorticoid (GC response, we hypothesized that polymorphic variants of the glucocorticoid receptor (GR gene might predispose for COPD and/or disease severity. Materials and methods Three out of about 50 of the most abundant receptor GR genepolymorphisms were investigated in a case-control study which included 207 patients with chronic bronchitis or COPD (mean FEV1 50.5% predicted, GOLD I-IV and 106 age matched healthy subjects (mean FEV1 101.8% predicted. These were genotyped: a for the N363S (Exon 2; 1220 A > G (I; b the BCLI restriction fragment length polymorphism (Intron 2; 647 C > G (II; and c the ER2223EK (Exon 2; 198, 200 G > A (III, using RT-PCR and PCR-RFLP method on genomic DNA isolated from EDTA blood. Results Genotype distribution between COPD and healthy subjects were alike in all of these three polymorphisms. N363S was found in 0.94% of the healthy and 0% of the COPD subjects. BCLI was detected in 11.3% of the controls and 15.5% of the COPD patients whereas heterozygote frequency was less in the COPD (44.4% group (controls 60.4%. ER2223EK lacks in any of the study subjects. Further, SNPs did not correlate with COPD severity stage (GOLD, exacerbation rates, and clinical course. Conclusion COPD is not linked to genepolymorphisms N363S, BCLI-RFLP, and ER2223EK. Since we analyzed only these 3 receptor genepolymorphisms, this study cannot rule out that other GR gene variants and linkages may be of influence.

Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor (TNF) gene and risk of endometriosis.However,the results remain controversial.Here we reviewed studies reporting the association between TNF genepolymorphisms and endometriosis risk in Asians.Methods PubMed and Embase were searched.Twelve case-control studies assessing the role of multiple TNF genepolymorphisms in endometriosis were included.If no less than two articles evaluated one variant,meta-analysis was conducted; otherwise,narrative analysis was chosen.A fixed-or random-effects model was employed according to the heterogeneity among studies.The strength of the association between TNF genepolymorphisms and endometriosis risk was assessed by odds ratios and 95％ confidence intervals.Results For TNF-α-238G＞A,-308G＞A,-857C＞T,and-863C＞A,no significant associations were identified from all genetic models.For TNF-α-850T＞C,results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT.For TNF-α-1031T＞C,a mild increase in endometriosis risk was found in the Asian population.Meta-analysis from two studies found that the TNF-β +252＞G polymorphism had a protective effect in Chinese individuals.Due to the limitations of the included studies,it is necessitated to perform more studies to elucidate the possible roles of TNF genepolymorphisms in the pathogenesis of endometriosis.Conclusions TNF-α-1031T＞C and TNF-β +252A＞G were significantly associated with the risk of endometriosis in Asian and Chinese populations,respectively.To further evaluate these associations,more large-scale,rigorously designed studies are needed.

Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 genepolymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population.

Schizophrenia is a chronic and neuropsychiatric disease that affects about 0.5-1% of the world's population. An increase in dopamine and dopamine D2 receptor (DRD2) gene products has been well described in schizophrenic patients. Several groups have studied the relationship between dopaminergic hyperactivity and cellular communications have obtained discordant results. Studies searching for the relationship between the schizophrenia and DRD2 gene have gained more interest. Our objective was to determine the relationships among schizophrenic symptoms in schizophrenia subtypes and severity of symptoms in terms of DRD2 gene -141C Insertion/Deletion [Ins/Del; I/D] polymorphism by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) assay method. Genomic DNA was prepared from peripheral blood by using salt extraction method. After amplification of genomic DNA, PCR products were digested with BstNI restriction enzyme for the detection of DRD2 gene -141C Ins/Del polymorphism in 73 schizophrenic patients and 60 healthy control subjects. The allelic frequencies of the DRD2 gene -141C Ins/Del polymorphism in case and control groups were 79.5 and 77.5% for I allele; 20.5 and 22.5% for D allele respectively. There was no significant difference in frequencies of genotypes and alleles between the two groups. In schizophrenic and control subjects, there were no significant relationship in severity of the disease and schizophrenia types among the -141C Ins/Del genotypes and alleles.

Full Text Available Abstract Background Recent research shows that polycystic ovary syndrome (PCOS may have an association with low-grade chronic inflammation, and that PCOS may induce an increase in serum interleukin-18 (IL-18 levels. Methods To investigate the polymorphisms of the IL-18 gene promoters with PCOS, two single nucleotide polymorphisms (SNPs in the promoter of the IL-18 gene (at positions -607C/A and -137G/C in 118 Chinese women with PCOS and 79 controls were evaluated using polymerase chain reaction (PCR. Results No significant differences were found in the genotype distribution, allele frequency and haplotype frequency between the PCOS and control groups. Further analysis demonstrated a relationship between IL-18 gene promoter polymorphisms and PCOS insulin resistance (IR. Regarding the -137 allele frequency, G and C allele frequencies were 93.5% and 6.5%, respectively, in the PCOS with IR patients; G and C allele frequencies were 85.4% and 14.6%, respectively, in PCOS patients without IR (chi2 = 3.601, P = 0.048. Conclusions The presence of a polymorphism in the IL-18 gene was found to have no correlation with the occurrence of PCOS. Carriage of the C allele at position -137 in the promoter of the IL-18 gene may play a protective role from the development of PCOS IR.

Full Text Available Autoimmune thyroid disease (AITD shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves’ disease (GD and Hashimoto’s thyroiditis (HT. The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility genepolymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations.

Autoimmune thyroid disease (AITD) shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility genepolymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations. PMID:28133421

The insulin-degrading enzyme (IDE) gene is a strong positional and biological candidate for late-onset Alzheimer disease (LOAD) susceptibility, with recent studies independently demonstrating an association between IDE gene variants and LOAD. However, previous data have been controversial. To investigate the relationship between IDE genepolymorphisms and LOAD risk, a case-control association study of 406 Han Chinese participants in Xinjiang, China, was undertaken. The LOAD and control groups consisted of 202 and 204 participants, respectively. The single-nucleotide polymorphisms rs1887922 and rs1999764 of the IDE gene were linked to LOAD incidence. The presence of the CT+CC genotype of rs1999764 had a protective effect compared to the TT genotype (adjusted P=.0001; odds ratio [OR]=0.226; 95% confidence interval [CI]=0.116-0.441), while the CT+CC genotype of rs1887922 was associated with increased LOAD risk (adjusted P=.0001; OR=3.640; 95% CI=1.889-7.016). Moreover, the effects of rs1887922 and rs1999764 were associated with LOAD risk independent of the apolipoprotein E ∊4 polymorphism and were more significant in men and women, respectively. These results demonstrate that the polymorphisms rs1887922 and rs1999764 of the IDE gene are associated with LOAD susceptibility in the Xinjiang Han population.

Much is known about the antiviral activity of Mx proteins in species such as mouse and human. In the mouse, loss of resistability to influenza virus has been shown to be due to specific polymorphisms in the Mx gene. This gene is therefore an interesting candidate gene for disease resistance in farm animals. The porcine Mx1 gene has already been identified and characterized based on its homology with mouse Mx1; however, until now no evidence of polymorphisms in the porcine gene has been reported. In this study, we have found two new polymorphisms in exon 14 of porcine Mx1 by DNA sequencing and confirmed their presence in different breeds, using polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) with NarI and NaeI restriction enzymes. On the basis of the deduced amino acid sequence, one allele contains a deletion that may result in a frameshift to yield several amino acid substitutions and extension of the carboxyl terminal region of Mx1 protein. The deletion allele, Mx1c, was found to be segregating in Landrace, Berkshire, Duroc, Hampshire, and Yucatan miniature pig. A second point mutation, Mx1b, was detected in Meishan and two Vietnamese native pig breeds. All other breeds tested were fixed for the Mx1a allele that is identical to the sequence reported previously. It will be interesting to determine if the Mx1c deletion is associated with variation in resistance to the myxovirus family in the pig.

Full Text Available Aim: Although the predictive and prognostic value of thymidylate synthase (TS expression and genepolymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS genepolymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.

The present study was aimed to evaluate serum leptin level and the frequency of oligopolymorphic codon 25 (CAA/CAG) of Ob gene in Behcet's disease. Eighty-seven patients with Behcet's disease and 85 healthy controls with matched age, gender and body mass index were included in the study. Serum leptin level was determined and genotype of codon 25 of Ob gene was performed by using the PCR amplification after DNA extraction. Serum leptin concentration of the patients with Behcet's disease (23.8 +/- 22.8 ng/ml) was higher than that of the control groups (17.1 +/- 14.7 ng/ml). The patients with Behcet's disease and control subjects showed CAA/CAA genotype, indicating the presence of no polymorphism. Neither Behcet's disease nor serum leptin level was found to be related to codon 25 polymorphism. We concluded that leptin 25CAG polymorphism is not associated with Behcet's disease and serum leptin level.

Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR genepolymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression. PMID:26578819

The studies on genepolymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

Objective: To explore the relationship between apolipoprotein E (ApoE) genepolymorphism and susceptibility of stress urinary incontinence (SUI).Methods: ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results: The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44% vs. 81.68%), while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls (10.00% vs. 9.90%). No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls (χ2=0.523, P=0.770).Conclusion: The genepolymorphism of ApoE is not independently involved in the development of SUI.

Full Text Available Natural resistance-associated macrophage protein (Nramp1 and the vitamin D receptor (VDR are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR genepolymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression.

In recent decades, increases have been observed in the incidence of nonmelanoma skin cancers, including basal cell carcinoma (BCC) and squamous cell carcinoma. BCC is the most common neoplasm in Caucasian populations. Sonic hedgehog (Shh) pathway impairment plays a key role in BCC pathogenesis, and there is evidence that Shh pathway genetic variations may predispose to BCC development. We genotyped 22 single-nucleotide polymorphisms (SNPs) in 4 Shh pathway genes: SHH, GLI, SMO, and PTCH. The study group consisted of 142 BCC patients and 142 age-matched, sex-matched healthy subjects (controls). SNPs were assessed using the PCR-RFLP method. The genotype distribution for the polymorphisms in the rs104894049 331 A/T SHH, rs104894040 349 T/C SHH, and rs41303402 385 G/A SMO genes differed significantly between the BCC patients and the controls. The presence of CC genotype in the SHH rs104894040 349 T/C polymorphism was linked to the highest risk of BCC development (OR 87.9, p polymorphisms showed no statistical differences between patients and controls. The results obtained testify to the importance of the SHH and SMO genepolymorphisms in skin cancerogenesis. These results mainly underline the potential role of SHH3 rs104894040 349 T/C genepolymorphism in the development of skin basal cell carcinomas in patients of Polish origin.

We aimed to examine the role of tumour necrosis factor gene complex polymorphisms in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized that individuals possessing polymorphic variants associated with higher tumour necrosis factor (TNF) secretion would be more susceptible to and/or have more severe disease. Patients with COPD and population controls underwent detailed clinical phenotyping. Genotyping for the tumour necrosis factor-308 and the lymphotoxin alpha NcoI (LTalpha polymorphisms was carried out by 'blinded' laboratory staff. Three hundred and sixty one individuals (220 cases and 141 controls) were recruited. We showed an association between the LTalphaNcol polymorphism and forced vital capacity (FVC) in a population of older adults with and without COPD. The LTalphaNcol*2 allele was associated with poorer lung function, under a codominant model, with a fall in FVC (expressed as a percentage of its predicted value) of 3.7% for each copy of the LTalphaNcol*2 allele possessed (for FVC, regression coefficient (95% CI)=-3.73(-7.01 to -0.44), P=0.026; for FEV(1) regression coefficient=-3.56(-7.80 to 0.70), P=0.101. However, there was no difference in genotype distribution between the case and control populations. This study adds weight to the suggestion that the TNF gene complex is involved in physiological alterations (FVC) that may affect the development and severity of COPD. The absence of a significant association between the TNF gene-complex polymorphisms in this study does not rule out a modest effect of these polymorphisms on the risk of COPD, as much larger studies are needed to detect modest gene effects on binary disease endpoints.

Protein Z has been reported to exert an important role in inhibiting coagulation. Polymorphisms in the protein Z gene (PROZ) may affect protein Z levels and thus play a role in thrombosis. This study aimed to investigate the prevalence and clinical significance of protein Z gene G79A polymorphism in Egyptian patients with systemic lupus erythematosus (SLE). We studied the distribution of the protein Z gene (rs17882561) (G79A) single-nucleotide polymorphism by PCR-restriction fragment length polymorphism in 100 Egyptian patients with SLE and 100 age, sex, and ethnically matched controls. There was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.103). But a statistically significant difference in the frequency of the alleles between SLE patients and controls was observed (P = 0.024). Also a significant association was detected between protein Z genotypes (and also A allele) and thrombosis, which is one of the manifestations of SLE (P = 0.004 and P = 0.001, respectively). Moreover, we observed a significant association between the protein Z AA and GA genotypes (and also A allele) and the presence of anticardiolipin antibodies (P = 0.016 and P = 0.004, respectively). The minor A allele of the G79A polymorphism in the protein Z gene might contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on some of the disease manifestations has been elucidated, so protein Z G79A AG/AA may be a risk factor for thrombosis.

Polymorphisms in several neurotransmitter-associated genes have been associated with variation in human personality traits. Among the more promising of such associations is that between the human dopamine receptor D4 gene (Drd4) variants and novelty-seeking behaviour. However, genetic epistasis, genotype-environment interactions and confounding environmental factors all act to obscure genotype-personality relationships. Such problems can be addressed by measuring personality under standardized conditions and by selection experiments, with both approaches only feasible with non-human animals. Looking for similar Drd4 genotype-personality associations in a free-living bird, the great tit (Parus major), we detected 73 polymorphisms (66 SNPs, 7 indels) in the P. major Drd4 orthologue. Two of the P. major Drd4 genepolymorphisms were investigated for evidence of association with novelty-seeking behaviour: a coding region synonymous single nucleotide polymorphism (SNP830) and a 15bp indel (ID15) located 5' to the putative transcription initiation site. Frequencies of the three Drd4 SNP830 genotypes, but not the ID15 genotypes, differed significantly between two P. major lines selected over four generations for divergent levels of 'early exploratory behaviour' (EEB). Strong corroborating evidence for the significance of this finding comes from the analysis of free-living, unselected birds where we found a significant association between SNP830 genotypes and differing mean EEB levels. These findings suggest that an association between Drd4 genepolymorphisms and animal personality variation predates the divergence of the avian and mammalian lineages. Furthermore, this work heralds the possibility of following microevolutionary changes in frequencies of behaviourally relevant Drd4 polymorphisms within populations where natural selection acts differentially on different personality types.

The authors report the chromosomal localization and a simple sequence repeat (SSR) in the cytosolic phospholipase A{sub 2} (cPLA{sub 2}) gene in both human and rat. A (CA){sub 18} repeat in the promoter of the rat gene was determined to exhibit length polymorphism when analyzed using the polymerase chain reaction (PCR) in 19 different inbred rat strains. Genotyping for this marker in 234 F{sub 2} progeny of a SHRXBN intercross mapped the gene to rat chromosome 13. Using a PCR strategy, a fragment of the promoter for the human gene was isolated, and a (CA){sub 18} repeat was identified. Since this marker displayed a low heterozygosity index, they also identified a mononucleotide repeat in the promoter for cPLA{sub 2} that displayed a polymorphism information content value of 0.76. The human gene was mapped using fluorescence in situ hybridization (FISH) to chromosome 1q25. Of interest, the gene encoding the enzyme prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), which acts on the arachidonic acid product of cPLA{sub 2}, was previously localized to this same chromosomal region, raising the possibility of coordinate regulation. Identification of intragenic markers may facilitate studies of polymorphic variants of these genes as candidates for disorders in which perturbations of the eicosanoid cascade may play a role. 20 refs., 3 figs., 2 tabs.

Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 genepolymorphisms have been related to increased susceptibility to cancer development in various organs. 261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (-196 to -174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene. As far as (-196 to -174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases. The -174 to -196del of TLR2 gene and Asp299Gly of TLR4 genepolymorphisms may confer an increased susceptibility to breast cancer development.

Full Text Available Eggshell quality is the main trait to assess egg quality. Marker assisted selection can be used to improve this trait. During eggshell formation, a mass of inorganic minerals is deposited. The Sodium Channel (SCNN1 gene family plays an essential role in cation transportation and SCNN1g is a member of this gene family. The objective of this study was to estimate the frequency of SCNN1g gene variants and to find its associations with eggshell quality in Hy-Line breed. 100 hens were randomly selected and their eggs and blood samples were collected. DNA was extracted and purified using the phenol-chloroform method and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP analysis. GLM procedure of SAS software was used to evaluate the association of SCNN1g genepolymorphism with egg weight, specific gravity, eggshell strength, eggshell weight, and eggshell thickness. Based on the polymorphism of SCNN1g gene, three genotypes were observed including AA, AG, and GG with frequencies of 0.26, 0.57, and 0.17, respectively. Genotype only had a significant effect on eggshell strength (P < 0.05. Other traits were not significantly influenced by genotypes of this gene. Therefore, introducing this gene in marker-assisted selection programs may improve eggshell strength of Hy-Line breed.

The angiotensin-converting enzyme (ACE) gene insertion or deletion in long-term hemodialysis patients may be associated with corrected QT interval prolongation, leading to fatal arrhythmias. The ACE D allele is known to increase the risk of malignant ventricular arrhythmias and is also associated with increased QT dispersion after myocardial infarction and hypertension. This study aimed to evaluate the relationship between ACE genepolymorphism and QT dispersion in hemodialysis patients. In 70 hemodialysis patients, electrocardiography was performed and QT dispersion was calculated. Corrected QT interval was calculated using Bazett Formula. The ACE genepolymorphism was determined by polymerase chain reaction. The mean age of the patients was 60 ± 12 years. The mean QT dispersion and corrected QT dispersion were 61.71 ± 21.99 and 73.18 ± 25.51, respectively. QT dispersion inversely correlated with serum calcium and potassium levels and positively correlated with ACE genepolymorphism and residual urine. Calcium level was the predictor factor for QT dispersion. The ACE genotype correlated with QT dispersion, corrected QT dispersion, hemoglobin, and residual urine, and inversely correlated with serum potassium. Corrected QT dispersion correlated with ACE genepolymorphism and residual urine. The DD genotype of ACE had significally greater QT dispersion and corrected QT dispersion than the II and ID genotypes. Our study showed that the most important parameter affecting corrected QT dispersion was ACE genepolymorphism on the background of D allelle. Patients carrying this allelle need special attention regarding optimal suppression of renin-angiotensin-aldosteron system activity.

@@ Patients with hypertension have the characteristics of abnormalities of vessel wall,blood constituents and blood flow. These abnormalities may confer a prothrombotic or hypercoagulable state and are related to the damage of target organs and long-term prognosis. Soluble thrombomodulin (sTM) as abnormalities of levels of specific plasma markers of endothelial damage or dysfunction may relate with the complications of hypertension and the determination of blood pressure itself. TM plays a critical role as a co-factor in the protein C pathway, 1 which is important in regulating coagulation as well as inflammation. Thus we hypothesized that the -33G＞A polymorphism alter thrombomodulin expression and/or impair anticoagulant function, which can predispose to the damage of the target organs during the progress of hypertension. Then, we investigated a possible association of sTM, TM on monocytes and the -33G＞A polymorphism with essential hypertension and cardiovascular disease (CVD) in the Chinese Han ethnic population.

Full Text Available Background: Single nucleotide polymorphism (SNPs are considered as one of the underlyingcauses of male infertility. Proper sperm chromatin packaging which involves replacement ofhistones with protamines has profound effect on male fertility. Over 20 SNPs have been reportedfor the protamine 1 and 2.Materials and Methods: The aim of this study was to evaluate the frequency of two previouslyreported SNPs using polymerase chain reaction (PCR-restriction fragment length polymorphism(RFLP approach in 35, 96 and 177 normal, oligozoospermic and azoospermic individuals. TheseSNPs are: 1. A base pair substitution (G at position 197 instead of T in protamine type 1 Openreading frame (ORF including untranslated region, which causes an Arg residue change to Serresidue in a highly conserved region. 2. cytidine nucleotide change to thymidine in position of 248of protamine type 2 ORF which caused a nonsense point mutation.Results: The two mentioned SNPs were not present in the studied population, thus concluding thatthese SNPs can not serves as molecular markers for male infertility diagnosis.Conclusion: The results of our study reveal that in a selected Iranian population, the SNP G197Tand C248T are completely absent and are not associated with male infertility and therefore theseSNPs may not represent a molecular marker for genetic diagnosis of male infertility.

Objective To analyze the correlation between the 3subtypes of PPAR genes (PPARα,PPARβ,and PPARγ) and the hypertriglyceridemic waist (HTGW) ,and to study whether there is an interaction in the 10 single nucleotide polymorphisms (SNPs) of the above 3 subtypes in causing HTGW.Methods Eight hundred and

Full Text Available Background: Chronic periodontitis is an inflammatory disease that causes rapid destruction of the tissues supporting the teeth. Genetic and environmental factors are involved in its occurrence. It has been suggested that IL-6 promoter genepolymorphism could affect the severity of chronic periodontitis. This study has examined the relationship between IL-6 (-174G/C genepolymorphism and chronic periodontitis.Materials and Methods: In this case-control study, 100 patients with chronic periodontitis and 100 healthy individuals referring to the clinic of Zahedan Dental School were evaluated. Two ml of peripheral blood was taken from these people. After DNA extraction through salting out method, IL-6 genepolymorphism was determined through T-ARMS-PCR technique using specific primers. The data were analyzed by chi-square test and p<0/05was considered significant.Results: The frequency of genotypes CC, GC, GG was respectively 61%, 35% and 4% in patients and respectively 67%, 31% and 2% in the control group. The frequency of G and C alleles was respectively 78.5% and 21.5% in the patient group, and respectively 82.5% and 17.5% in control group. No statistically significant difference was observed between the two groups in frequency of genotypes and alleles.Conclusion: This study showed no correlation between IL-6-174 G/C genepolymorphism and chronic periodontitis.

Full Text Available Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator genepolymorphisms and the incidence of stroke in patients with essential hypertension (EH. The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects. Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation. The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92, whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83. As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8(IL8 genes, although no association between these loci and stroke was detected by individual analysis.

Full Text Available Malignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability.

Genetic polymorphisms in some DNA repair proteins are associated with a number of malignant transformations like head and neck squamous cell carcinoma (HNSCC). Xeroderma pigmentosum group D (XPD) and X-ray repair cross-complementing proteins 1 (XRCC1) and 3 (XRCC3) genes are involved in DNA repair and were found to be associated with HNSCC in numerous studies. To establish our overall understanding of possible relationships between DNA repair genepolymorphisms and development of HNSCC, we surveyed the literature on epidemiological studies that assessed potential associations with HNSCC risk in terms of gene–environment interactions, genotype-induced functional defects in enzyme activity and/or protein expression, and the influence of ethnic origin on these associations.We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of HNSCC when DNA repair capacity is reduced.

The aim of the study was to test MYO9B genepolymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control co

We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment.…

Full Text Available In ischemic stroke, extracranial MR angiography (ECMRA is more frequently abnormal in Caucasians and intracranial (ICMRA in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D genepolymorphism and its correlation with MRA findings in patients with ischemic stroke.

Association of vitamin D receptor (VDR) genepolymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) genepolymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI genepolymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI genepolymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.

Full Text Available Background: The aim of this study was to investigate the association between LAPTM4B genepolymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer.

textabstractPolymorphisms of the OXTR gene affect people's social interaction styles in various social encounters: carriers of the OXTR GG, compared to the OXTR AA/AG in general, are more motivated to interact socially and detect social salience. We focus on sales professionals operating in knowledg

textabstractBackground: Individual variations in gastric cancer risk have been associated in the last decade with specific variant alleles of different genes that are present in a significant proportion of the population. Polymorphisms may modify the effects of environmental exposures, and these

Self-regulatory behavior in early childhood is an important characteristic that has considerable implications for the development of adaptive and maladaptive functioning. The present study investigated the relations between a functional polymorphism in the upstream region of monoamine oxidase A gene (MAOA) and self-regulatory behavior in a sample…

The objective was to determine if single nucleotide polymorphisms (SNPs) in porcine MX2 gene affect its antiviral potential. MX proteins are known to suppress the multiplication of several viruses, including influenza virus and vesicular stomatitis virus (VSV). In domestic animals possessing highly polymorphic genome, our previous research indicated that a specific SNP in chicken Mx gene was responsible for its antiviral function. However, there still has been no information about SNPs in porcine MX2 gene. In this study, we first conducted polymorphism analysis in 17 pigs of MX2 gene derived from seven breeds. Consequently, a total of 30 SNPs, of which 11 were deduced to cause amino acid variations, were detected, suggesting that the porcine MX2 is very polymorphic. Next, we classified MX2 into eight alleles (A1-A8) and subsequently carried out infectious experiments with recombinant VSVΔG*-G to each allele. In A1-A5 and A8, position 514 amino acid (514 aa) of MX2 was glycine (Gly), which did not inhibit VSV multiplication, whereas in A6 and A7, 514 aa was arginine (Arg), which exhibited the antiviral ability against VSV. These results demonstrate that a SNP at 514 aa (Gly-Arg) of porcine MX2 plays a pivotal role in the antiviral activity as well as that at 631 aa of chicken Mx.

Objective:To investigate the correlation between STAT3 genepolymorphisms and endometriosis complicated with infertility.Methods: A total of 35 patients with endometriosis complicated with infertility and 35 cases of healthy volunteer from October 2014 to October 2015 in our hospital were selected as research objects. STAT3 genepolymorphisms of all objects were detected by PCR-RFLP method.Results: Polymorphic sites of STAT3 gene rs2293152 were expressed as three genotypes, namely, CC, GC, and GG. There were 18 cases, 10 cases and 7 cases of type CC, GC and GG in the observation group, accounted for 51.43%, 28.57% and 20.00%, respectively. There were 29 cases, 3 cases and 3 cases of type CC, GC and GG in the control group, accounted for 82.86%, 8.57% and 8.57%. There was a statistically difference` between the two groups. The frequency of C and G allele in the observation group and the control group were 65.71%, 34.29% and 87.14%, 12.86%, respectively. There were statistically significant differences between two groups. In addition, compared with the CC genotype, genotype G might increase the risk of the disease.Conclusions:The susceptibility of endometriosis complicated with infertility may be associated with STAT3 genepolymorphism and women who carried the G allele may have an increased the risk of the disease.

Behçet's disease (BD) is a multi-systemic vasculitis. The aim of this study was to investigate the association between Rho-kinase (ROCK2) genepolymorphisms and patients with BD in a Turkish population. A total of 194 BD patients and 276 healthy controls with similar age and sex were included to this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. mRNA from blood samples was extracted, and real-time polymerase chain reaction was performed for ROCK2 gene expression. There were marked changes in both genotype (TT, 41.8%; TA, 30.3%) and allele (T, 57%; A, 43%) frequencies for the rs35768389 (Asp601Val) polymorphism in patients compared with controls (TT, 64.6%; TA, 9.4%, P ROCK2 expressions in patients. This is the first study to examine the involvement of ROCK2 gene variation in the risk of incident BD. The results strongly suggest that ROCK2 genepolymorphisms may modify individual susceptibility to BD in the Turkish population.

This study was conducted to investigate polymorphism of the coagulase gene of Staphylococcus aureus causing bovine mastitis. One hundred eighty-seven strains of S. aureus were isolated from bovine mastitic milk samples obtained from 187 different Danish dairy farms. The isolates were characterised...

OBJECTIVE: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic

Conclusion: Therefore, the promoter polymorphisms in cytokine genes can be used as biomarkers to predict cervical cancer susceptibility in a north Indian population. However, such studies need to be carried out in different ethnic populations in order to discover the specific risk alleles, genotypes and combinations for disease prediction.

Four (CA), repeats, located in introns,44,45,49 and 50 of the dystrophin gene,were evaluated in Chinese.These loci are highly polymorphic,with polymorphism information contents of 0.872,0.772,0.870 and 0.718,respectively.All four loci can be easily amplified and labelled using two duplex PCR reactions with α-32P-dCTP and can be detected by denaturing polyacrylamide gel electrophoresis.Using these four loci and the two polymorphic(CA)n repeats located at the 5′ and 3′ ends of the dystrophin gene,we have developed a new PCR-based procedure-Amp-FLP( amplified fragment length polymorphism)linkage analysis for the gene diagnosis of DMD/BMD.This method can detect intragenic recombination rapidly and efficiently and greatly improves the success rate of carrier deterction and prenatal diagnosis in non-deletion DMD/BMD families.All of the loci used in this procedure are intragenic.In addition ,the loci in introns 44,45,49 and 50 are located in the deletion-prone region of the dystrophin gene,making them valuable and usefui in the identification of deletion mutations.Here we report one case of deletion detection using these four loci.

Leptin is a hormone produced by adipocytes, and its expression is regulated by body fatness and energy balance. This study describes the association of four leptin genepolymorphisms in dairy cows (R4C, A59V, RFLP1, and BM1500) with circulating leptin concentrations during the periparturient period.

Interleukin (IL)-1alpha IL-1beta, and IL-1ra contribute to regulation of the inflammatory response in periodontal tissues. We aimed to investigate the distribution of polymorphisms in the IL-1 gene family among periodontitis patients and controls, taking into account smoking and microbiology as addi

Objective: To examine whether polymorphism within the tumor necrosis factor α（TNFα） gene is associated with the susceptibility and clinic manifestations to systemic lupus erythe matosus （SLE） in the patients of Han ethnic group collected from the Northern China. Methods: TNF1 and TNF2 subtypes

Susceptibility to scrapie in sheep is influenced by polymorphisms of the prion protein (PrP) gene, whereas no strong association between genetics and scrapie has yet been determined in goats due to the limited number of studies on these animals. In this case¿control study on 177 goats from six Itali

Full Text Available PURPOSE: Varicoceles are associated with impaired testicular function and male infertility, but the molecular mechanisms by which fertility is affected have not been satisfactorily explained. Spermatogenesis might be affected by increased scrotal temperature, such as that caused by varicocele. HSP90 is a molecular chaperone expressed in germ cells and is related to spermatogenesis, motility, and both heat and oxidative stress. Possible correlations between coding single region nucleotide polymorphisms (cSNPs in the HSP90 gene in patients with varicocele associated with infertility were analyzed, and polymorphisms in these exons were characterized through DNA sequencing. MATERIALS AND METHODS: PCR-SSCP and DNA sequencing were used to search for mutations in 18 infertile patients with varicocele, 11 patients with idiopathic infertility and 12 fertile men. DNA was extracted from leucocytes for PCR amplification and SSCP analysis. DNA from samples with an altered band pattern in the SSCP was then sequenced to search for polymorphisms. RESULTS: Three silent polymorphisms that do not lead to amino acid substitutions were identified. CONCLUSION: Mutations in the HSP90 gene do not appear to be a common cause of male factor infertility. The low incidence of gene variation, or SNPs, in infertile men demonstrates that this gene is highly conserved and thus confirms its key role in spermatogenesis and response to heat stress.

The aim of this study was to investigate the predictive impact of polymorphisms in the HIF-1α gene on the response to chemoradiotherapy (CRT) in rectal cancer. This study included two cohorts of patients with locally advanced rectal cancer receiving long-course CRT. The HIF-1α C1772T (rs11549465...

Leptin is a hormone produced by adipocytes, and its expression is regulated by body fatness and energy balance. This study describes the association of four leptin genepolymorphisms in dairy cows (R4C, A59V, RFLP1, and BM1500) with circulating leptin concentrations during the periparturient period.

Objective To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes(CYP2C19,ABCB1 and PON1) in Chinese patients with acute coronary syndrome(ACS) by genotype analysis. Methods Genetic analysis was performed in patients admitted to

textabstractAims: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug. Methods: This was a cohort study among 239 subjects who

AIMS: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug. METHODS: This was a cohort study among 239 subjects who started ACE

Polymorphisms in the coding region of the prion protein gene (PRNP) have been associated with the susceptibility and incubation period of prion diseases in humans and sheep. However, polymorphisms in this part of the bovine PRNP gene do not affect the classical bovine spongiform encephalopathy (BSE) susceptibility in cattle. Studies carried out in Germany have shown that insertion/deletion-type polymorphisms located in the promoter region of the bovine prion gene are possible genetic factors modulating BSE susceptibility by changing the level of PRNP expression. No such association was observed for atypical BSE cases; however, due to the rare nature of the disease, these results should be confirmed. Additionally, a single nonsynonymous mutation in PRNP codon 211 (E211K) was described in one H-type BSE case in the USA; however, it was not found in any other cases. Here, we performed genetic characterization of PRNP promoter indel variations and determined the polymorphism of open reading frames (ORFs) of PRNP and bovine prion-like Shadoo (SPRN) genes in six Polish atypical BSE cases and compared these results to the population of clinically healthy Polish Holstein cattle. No potentially pathogenic mutations were found in the PRNP ORF in atypical BSE-affected cattle, but our study showed a high frequency of deletions at the indel loci of PRNP promoter in these animals. Additionally, a rare sequence variation in the SPRN protein-coding sequence was found in one L-type atypical BSE-affected animal.

Full Text Available The distribution of the T29C TGFβ1 genepolymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 genepolymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 genepolymorphism, prevalence of TC or CC genotypes was significantly (Pgene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension.

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986-2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986–2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

Full Text Available OBJECTIVE: The present study evaluated the association between lactotransferrin (LTF genepolymorphism (exon 2, A/G, Lys/Arg and dental caries. MATERIAL AND METHODS: A convenience sample of 110 individuals, 12 years old, was divided into: group 1, 48 individuals without caries experience (DMFT=0, and group 2, 62 subjects with caries experience (DMFT>1. DNA was obtained from a mouthwash with 3% glucose solution, followed by a scrapping of the oral mucosa. After DNA purification, polymerase chain reaction (PCR, single strand conformation polymorphism (SSCP was performed to access the study polymorphism. The LTF A/G (Lys/Arg polymorphism had been previously reported as located in exon 1. RESULTS: Allele 1 of the study polymorphism was associated with low DMFT index and showed a protective effect against caries experience (OR=0.16, IC=0.03-0.76, p=0.01. CONCLUSIONS: Lactotransferrin A/G (exon 2, Lys/Arg polymorphism was associated with susceptibility to dental caries in 12-year-old students.

Full Text Available The aim of this study was to test the possible implication of toll-like receptor 2 (TLR2 and TLR4 genepolymorphisms in determining the susceptibility to Chagas' disease. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 475 individuals from Colombia, 143 seropositive with chagasic cardiomyopathy, 132 seropositive asymptomatic and 200 seronegative. The TLR2 arginine to glutamine substitution at residue 753(Arg753Gln polymorphism was absent in the groups analyzed. The TLR4 Asp299Gly and Thr399Ile polymorphisms are in linkage disequilibrium and we observed a very low frequency of these polymorphisms in our study population (2.6% and 1.8% respectively. The overall TLR2 and TLR4 alleles and genotype distribution in seronegative and seropositive were not significantly different. We compared the frequencies between asymptomatic patients and those with chagasic cardiomyopathy and we did not observe any significant differences in the distribution of alleles or genotypes. In summary, this study corroborates the low frequency of TLR2 and TLR4 polymorphisms observed in other populations and suggest that these do not play an important role in Chagas' disease. The validation of these findings in independent cohorts is needed to firmly establish a role for TLR2 and TLR4 variants in Chagas' disease.

We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 genepolymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Science was conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6 polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/T polymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/T polymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis.

Full Text Available BACKGROUND: Carrot is a vegetable cultivated worldwide for the consumption of its root. Historical data indicate that root colour has been differentially selected over time and according to geographical areas. Root pigmentation depends on the relative proportion of different carotenoids for the white, yellow, orange and red types but only internally for the purple one. The genetic control for root carotenoid content might be partially associated with carotenoid biosynthetic genes. Carotenoid isomerase (CRTISO has emerged as a regulatory step in the carotenoid biosynthesis pathway and could be a good candidate to show how a metabolic pathway gene reflects a species genetic history. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the nucleotide polymorphism and the linkage disequilibrium among the complete CRTISO sequence, and the deviation from neutral expectation were analysed by considering population subdivision revealed with 17 microsatellite markers. A sample of 39 accessions, which represented different geographical origins and root colours, was used. Cultivated carrot was divided into two genetic groups: one from Middle East and Asia (Eastern group, and another one mainly from Europe (Western group. The Western and Eastern genetic groups were suggested to be differentially affected by selection: a signature of balancing selection was detected within the first group whereas the second one showed no selection. A focus on orange-rooted carrots revealed that cultivars cultivated in Asia were mainly assigned to the Western group but showed CRTISO haplotypes common to Eastern carrots. CONCLUSION: The carotenoid pathway CRTISO gene data proved to be complementary to neutral markers in order to bring critical insight in the cultivated carrot history. We confirmed the occurrence of two migration events since domestication. Our results showed a European background in material from Japan and Central Asia. While confirming the introduction of European

The Leu7Pro polymorphism in the signal peptide of the preproneuropeptide Y (NPY) has been associated with dyslipidemias and free fatty acid (FFA) levels during exercise. The association of this polymorphism with insulin sensitivity has not been studied. In this study, the Leu7Pro polymorphism was determined in 2 groups of nondiabetic middle-aged subjects (n = 266 and n = 295). Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp (n = 266) or with an intravenous glucose tolerance test (IVGTT, n = 295). First-phase insulin secretion was determined as insulin area under the curve (AUC) during the first 10 minutes of the IVGTT. FFAs were measured both in the fasting state and during the hyperinsulinemic clamp. The Leu7Pro polymorphism of the NPY gene was not associated with the rates of whole body glucose uptake, insulin sensitivity index, insulin secretion during the IVGTT, or insulin AUC during the oral glucose tolerance test. However, the Pro7 allele was associated with low FFA levels both in the fasting state (P =.043) and during the hyperinsulinemic clamp (P =.003). In conclusion, the Leu7Pro polymorphism of the NPY gene associates with alterations in FFA metabolism but does not have an impact on insulin sensitivity, insulin secretion, or glucose metabolism. Copyright 2003 Elsevier Inc. All rights reserved.

The purpose of this study was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor 1 gene (ESR1) at rs2234693 and rs9340799, as well as to investigate the relationship between ESR genepolymorphisms and postmenopausal osteoporosis (OP) of the spine in Chinese women. We recruited 198 postmenopausal women with OP and 276 healthy women between May 2012 and September 2015 in Zhongshan Hospital. Dual energy x-ray absorptiometry was used to measure the bone mineral density (BMD) of the lumbar vertebrae in all subjects. In addition, PCR-restriction fragment length polymorphism based analysis was conducted to identify the genotypes of ESR1. The distribution of ESR1 in the osteoporosis group and the control group was determined; the relationship between ESR polymorphisms and BMD was analyzed. The distributions of BMD were: TT < TC < CC, GG < AG < AA. The TT, TTGG, and TCGG genotypes were found to be lower as compared to the other genotypes. Stratified analysis suggested that the TT genotype and the combined genotypes TTGG and TCGG were significantly higher in the OP group as compared to the control group (P < 0.01). Therefore, ESR1 polymorphisms at rs2234693 and rs9340799 may be associated with OP, and could be used as markers to screen those with high risks to postmenopausal OP in Chinese women.

AIM: Recent studies suggest that Fas-mediated apoptosis is involved in the pathogenesis of inflammatory bowel disease (IBD). It has been hypothesized that either increased apoptosis of intestinal epithelium or decreased apoptosis of lamina propria lymphocytes may induce inflammation of gut. The aim of this study was to determine whether the Fas gene promoter polymorphism at position-670 was associated with IBD in Chinese patients.METHODS: Fifty unrelated Chinese patients with IBD (38patients with ulcerative colitis and 12 with Crohn's disease)and 124 healthy controls were genotyped for the Fas-670polymorphism by PCR-restriction fragment length polymorphism method. The PCR product was digested by Mva I restriction enzyme.RESULTS: Distribution of the Fas-670 genepolymorphism was 33% for the AA genotype, 52% for the AG genotype and 15% for the GG genotype in 124 healthy subjects. In patients with IBD, 30% was for the AA genotype, 42% for the AG genotype and 28% for the GG genotype respectively. However, there was no significant difference in the genotype (P= 0.1498), allele frequencies (P= 0.3198)and carriage frequencies (P = 0.4133) between healthy controls and IBD patients. Furthermore, we did not find any difference between the left-sided colitis and total colitis (P = 0.8242).CONCLUSION: Fas-670 polymorphism is not associated with IBD in Chinese patients.

The Glu298Asp polymorphism in the NOS3 gene has been implicated as a risk factor for prostate cancer. To date, several studies have evaluated the associations between the Glu298Asp polymorphism and prostate cancer risk; however, the results were inconclusive. The aim of the current study was to perform a meta-analysis to investigate the association between the polymorphism and the risk of prostate cancer. A total of 3,206 cases and 3,880 controls from eight case-control studies were included for data synthesis. The overall results suggested no significant association between the polymorphism and the risk of prostate cancer (OR=1.01, 95% CI=0.92-1.11, p = 0.83 for Asp/Asp+Glu/Asp vs. Glu/Glu). In the stratified analysis according to ethnicity, no significant associations were observed in Asians and Europeans. The current meta-analysis suggested that the Glu298Asp polymorphism of the NOS3 gene might not contribute to the risk of prostate cancer.

Full Text Available Background: P-glycoprotein (P-gp, a drug efflux transporter, encoded by the gene MDR1 ABCB1 multidrug resistant, reduces the penetration through the brain by the AEDs. Overexpression of Pgp in blood-brain barrier in epileptic patients play an important rol in pharmacoresistance. The aim of this study was to evaluate a possible association between C1236T and G2677T ABCB1 genepolymorphisms and drug-resistant epilepsy in Romanian children.

Objective IgA nephropathy is one of the most com- mon form of primary glomerulonephritis throughout the world and a main renal disease which causes renal failure. P-selectin plays an important role in the pathogenesis and development of IgA nephropathy. The purpose of this study is to find a possible relationship between P-selectin genepolymorphism and IgA nephropathy. Methods In this study,a comprehensive P-selectin gene sur-

Full Text Available BACKGROUND: Two polymorphisms, -260C/T and -651C/T, in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. This meta-analysis aimed to investigate the association between the two polymorphisms and risk of cancer. METHODS: All eligible case-control studies published up to March 2014 were identified by searching PubMed, Web of Science, CNKI and WanFang database. Pooled odds ratio (OR with 95% confidence interval (CI were used to access the strength of this association in fixed- or random-effects model. RESULTS: 17 case-control studies from fourteen articles were included. Of those, there were 17 studies (4198 cases and 4194 controls for -260C/T polymorphism and three studies (832 cases and 1190 controls for -651C/T polymorphism. Overall, no significant associations between the two polymorphisms of CD14 gene and cancer risk were found. When stratified by ethnicity, cancer type and source of control, similar results were observed among them. In addition, in further subgroups analysis by Helicobacter pylori (H. pylori infection status and tumor location in gastric cancer subgroup, we found that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. CONCLUSIONS: This meta-analysis suggests that the CD14 -260C/T polymorphism may increase the risk of gastric cancer in H. pylori-infected individuals. However, large and well-designed studies are warranted to validate our findings.

The susceptibility loci of ERAP1 polymorphisms have been found to be strongly associated with ankylosing spondylitis (AS). The researches in multiple ethnic cohorts suggested that the population attributable risk in ERAP1 polymorphisms is at a high significance level. This study was undertaken to estimate the prevalence and incidence of subsets of AS and investigate the specific variants of ERAP1 polymorphisms in AS susceptibility, in the Han ethnic Chinese population in Zhejiang Province. AS patients were selected, diagnosed, and confirmed by a qualified rheumatologist. The basal clinical and demographic characteristics were compared with all subjects. Genotypes for eight selected single nucleotide polymorphisms (SNPs) in ERAP1 gene (rs27038, rs27037, rs27434, rs27980, rs7711564, rs30187, rs10050860, and rs17482078) were determined by using the Sequenom MassARRAY iPLEX platform in Zhejiang Han Chinese population. Association analyses were performed on the whole genotyped data set in 707 unrelated ankylosing spondylitis cases and 837 ethnically matched controls. We observed the strongest association between AS and HLA-B27, which confers over 90 % of ankylosing spondylitis cases. Moreover, we found three loci of ERAP1 polymorphisms were at a high significance level (rs27037 P = 0.00451; rs27434 P = 0.00012; rs27980 P = 0.00682) with AS in Zhejiang population. We also confirmed polymorphism locus of ERAP1 previously reported association with AS (rs27434; P = 5.3 × 10(-12)). Our results indicated a difference in the mechanism of susceptibility loci in subsets of Zhejiang Han Chinese population and provided further evidence that rs27434 is the key polymorphism associated with AS in ERAP1 gene.

Full Text Available Purpose. We investigated the association between genotypes and haplotypes of the c.-61G>T (rs 1801320 and c.-98G>C (rs 1801321 polymorphisms of the RAD51 gene and the occurrence of keratoconus (KC and Fuchs endothelial corneal dystrophy (FECD in dependence on some environmental factors. Methods. The polymorphisms were genotyped in peripheral blood lymphocytes of 100 KC and 100 FECD patients as well as 150 controls with PCR-RFLP. Results. The G/T genotype of the c.-61G>T polymorphism was associated with significantly increased frequency occurrence of KC (crude OR 2.99, 95% CI 1.75–5.13. On the other hand, the G/G genotype of this polymorphism was positively correlated with a decreased occurrence of this disease (crude OR 0.52, 95% CI 0.31–0.88. We did not find any correlation between genotypes/alleles of the c.-98G>C polymorphism and the occurrence of KC. We also found that the G/G genotype and G allele of the c.-98G>C polymorphism had a protective effect against FECD (crude OR 0.51, 95% CI 0.28–0.92; crude OR 0.53, 95% CI 0.30–0.92, resp., while the G/C genotype and the C allele increased FECD occurrence (crude OR 1.85, 95% CI 1.01–3.36; crude OR 1.90, 95% CI 1.09–3.29, resp.. Conclusions. The c.-61T/T and c.-98G>C polymorphisms of the RAD51 gene may have a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.

This study was designed to examine a single nucleotide polymorphism (SNP) in the HIF-3α gene in three hundred Changbaishan black cattle using PCR-restriction fragment length polymorphism to determine whether there is an association between this SNP and superovulation. The cloning and sequencing results indicate that the polymorphism is due to a point mutation at the 278-bp position in the HIF-3α gene, resulting in 3 genotypes (AA, AB, and BB). Association analysis indicated that the polymorphism has a significant effect on the number of unfertilized embryos (NUE) (P superovulation improvement, and assisted fertility.

Full Text Available The aim of the research is to analyse the influence of polymorphisms of endothelin-1 gene and endothelin-1 receptor type A gene on the clinical condition of patients with primary open angle glaucoma. Methods. 285 Polish patients took part in the research (160 normal-tension glaucoma and 125 high-tension glaucoma. DNA was isolated by standard methods and genotype distributions of four polymorphisms in genes encoding endothelin-1 (K198N and endothelin-1 receptor type A polymorphisms (C1222T, C70G, and G231A were determined. Genotype distributions were compared between NTG and HTG groups. The clinical condition of participants was examined for association with polymorphisms. Results. A similar frequency of occurrence of the polymorphic varieties of the studied genes was observed in patients with NTG and HTG. There is no relation between NTG risk factors and examined polymorphisms. NTG patients with TT genotype of K198N polymorphism presented with the lowest intraocular pressure in comparison to GG + GT genotype (p=0.03. In NTG patients with CC genotype of C1222T polymorphism (p=0.028 and GG of C70G polymorphism (p=0.03 the lowest values of mean blood pressure were observed. Conclusions. The studied polymorphic varieties (K198N, C1222T do have an influence on intraocular pressure as well as arterial blood pressure in NTG patients.

Interleukins (IL) 4 and 13 genes and their receptors (R) are the key cytokines which amplify inflammatory reactions in asthma. This study aimed to investigate the association of IL 4, 4 R, 13 and 13 R genespolymorphism with asthma in Indian children. In this hospital-based case-control study, included were children aged 1-15 years recruited as diagnosed cases of bronchial asthma, according to EPR 2007 and excluded were subjects with other respiratory diseases. Children with no present or past history of asthma were enrolled as controls. Spirometry was done in cases age ≥ 6 years. Gene-gene interaction was evaluated using binary logistic regression. From October 2010 to July 2013, 275 cases and 275 controls were recruited. Gene-gene interactions between C1112T in IL 13 and Ile50Val in IL 4 R genepolymorphisms were found to be statistically significant (OR = 2.37, 95% CI = 1.04-5.42, p = 0.040). Individuals with CT and GG genotype of C1112T in IL 13 and Ile50Val in IL 4 R were at twice the risk for the development of asthma compared to individuals with both non-risk genotypes. The data suggests that gene-gene interactions between IL 13 and IL 4 R genes may play an important role in asthma among Indian children.

Jun 11, 2014 ... environmental stress through investigating SOD and PAL gene expression and also the genetic relationship .... obtained from the gene bank (www.ncbi.gov) under accession number ... stored at -20°C for further work. Primers ...

Full Text Available Objective To investigate the correlation between the polymorphism of angiotensin converting enzyme(ACE gene I/D and angiotensin converting enzyme 2(ACE2 gene A9570G and atrial fibrillation.Methods In chronological order of hospitalization,305 patients were selected and divided into two groups: atrial fibrillation group(148 cases and control group(157cases without atrial fibrillation.The control group was matched with the atrial fibrillation group in terms of age,gender,and presence of left ventricular dysfunction,coronary heart disease,diabetes,and primary hypertension.The polymorphisms of the ACE gene I/D and ACE2 gene A9570G were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP and gene sequencing approach.Results There were no statistical differences between the atrial fibrillation group and the control group in genotype distribution and allele frequencies of the ACE gene I/D(P=0.841;OR=0.948,95% CI 0.680-1.322,P=0.755.Moreover,there was no significant difference among the different genotypes of ACE gene I/D in the left and right atrial dimensions(P=0.887 and P=0.664,respectively.In the male subgroup,there was no statistical difference in the ACE2 gene A9570G polymorphism between the two groups(OR=1.631,95% CI 0.880-3.023,P=0.119.However,in the subgroup of males with atrial fibrillation,the left and right atrial dimensions of subjects with G genotype(40.1±6.4 and 40.1±5.7mm,respectively were larger than those with A genotype(37.0±4.4 and 36.5±4.4mm,respectively,indicating a statistical difference(P=0.028,P=0.010.In the female subgroup,there were no statistical differences between the atrial fibrillation group and the control group in the genotype distribution and allele frequencies of the ACE2 gene A9570G polymorphism(P=0.286;OR=1.415,95% CI 0.885-2.264,P=0.146.In the subgroup of females with atrial fibrillation,no significant difference was found in the left or right atrial dimension among the

The establishment of an association between prion protein gene (PRNP) polymorphisms and scrapie susceptibility in sheep has enabled the development of breeding programmes to increase scrapie resistance in the European Union. Intense selection for PRNP genotype may lead to correlated selection for genes linked to PRNP. We intended to investigate if any association exists between genetic variation in prion-like protein Doppel gene (PRND) and scrapie susceptibility, determined through PRNP genotyping. Sampling included 460 sheep from eight Portuguese breeds and the PRND gene coding region was analysed by multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP), whereas PRNP genotyping was carried out by primer extension. A synonymous substitution (c.78G>A) was detected in codon 26 of the PRND gene, in all breeds except Churra Mondegueira. Linkage disequilibrium was found between the PRND and PRNP loci (P = 0.000). Specifically, PRND was monomorphic in the 45 animals with the more resistant ARR/ARR PRNP genotype (P = 0.003), whereas a higher frequency of PRND heterozygotes (GA) was associated with ARQ/AHQ (P = 0.029). These results constitute preliminary evidence of an association between a polymorphism in the PRND gene and scrapie susceptibility, and indicate that the possibility of undesirable consequences from widespread selection for PRNP genotype on genetic diversity and reproduction traits needs to be further investigated.

The authors assessed the genepolymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), A/u-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes of these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.

Full Text Available Genetic and environmental factors have an influence on the process of growth and development of the body. One of numerous genetic factors can be the vitamin D receptor gene (VDR. The study aimed at evaluating the relationship between VDR polymorphism and somatic parameters in children.Patients and methods: The study group consisted of 395 children, aged 6–18 years. All the patients underwent gene typing using the PCR-RFLP method within polymorphic loci BsmI (rs1544410, FokI (rs2228570, ApaI (rs7975232 and TaqI (rs731236 of the VDR receptor gene. 294 children made up the control group in the study on the incidence of particular genotypes; in 161 patients somatic measurements of body weight and height were made with standard methods and skeletal densitometry (total body and spine programmes examination was performed. Statistica 10.0 PL was used for statistical analysis.Results: In patients with low bone mass a relationship between body height and FokI VDR polymorphism was noted. The p-value was statistically significantly different in group I (p=0.002 and borderline significant in group III (p=0.09. None of the polymorphisms of the VDR receptor gene demonstrated any statistically significant differences in anthropometric values in the control group and in children with osteoporosis.Summary: The presence of the F allele of FokI polymorphism of the VDR receptor gene results in increased height, which is best observed in children with low bone mass. The FF genotype favours increased height in the study group of children from Łódź.

Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) genepolymorphism in Chinese hypertensive subjects. Methods Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. Results Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD>ID>II, P0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%, and 79.5% vs 40.5%, respectively, P<0.001). In multiple stepwise regression analysis, independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes (P<0.001), age (P<0.001) and carotid internal diameter (P=0.032). Moreover, triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype (P<0.05). Conclusions The I/D polymorphism of the ACE gene was related to IMT, but not to internal diameter, distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE genepolymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.

Patients with sickle cell disease (SCD) produce significantly low levels of plasma nitric oxide (NO) during acute vaso-occlusive crisis. In transgenic sickle cell mice, NO synthesized by endothelial nitric oxide synthase (eNOS) enzyme of vascular endothelial cells has been found to protect the mice from vaso-occlusive events. Therefore, the present study aims to explore possible association of eNOS genepolymorphism as a potential genetic modifier in SCD patients. A case control study involving 150 SCD patients and age- and ethnicity-matched 150 healthy controls were genotyped by PCR-restriction fragment length polymorphism techniques for three important eNOS genepolymorphisms-eNOS 4a/b, eNOS 894G>T and eNOS -786T>C. It was observed that SCD patients had significantly higher frequencies of mutant alleles besides heterozygous and homozygous mutant genotypes of these three eNOS genepolymorphisms and low levels of plasma nitrite (NO2) as compared with control groups. The SCD severe group had significantly lower levels of plasma NO2 and higher frequencies of mutant alleles of these three SNPs of eNOS gene in contrast to the SCD mild group of patients. Haplotype analysis revealed that frequencies of one mutant haplotype '4a-T-C' (alleles in order of eNOS 4a/b, eNOS 894G>T and eNOS -786T>C) were significantly high in the severe SCD patients (Phaplotype '4b-G-T' was found to be significantly high (P<0.0001) in the SCD mild patients, which indicates that eNOS genepolymorphisms are associated with SCD patients in India and may act as a genetic modifier of the phenotypic variation of SCD patients.

The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development.The aim of this study was to determine the possible association between VDR genepolymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal.A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history.SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms.Our study confirms a possible role of VDR genepolymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of Taq

BACKGROUND:Studies addressing the correlation between prion protein gene codon 129 polymorphism,Alzheimer's disease,and cognitive disorders have mainly focused on Caucasians.However,prion protein gene codon 129 polymorphism is thought to also affect the Chinese Han and Wei populations.OBJECTIVE:To analyze the differences of prion protein gene codon 129 distribution among the elderly Chinese Han,East Asian,and Caucasian populations,and to study the correlation between prion protein gene codon 129 distribution and late-onset Alzheimer's disease.DESIGN,TIME AND SETTING:A genepolymorphism analysis was performed in the Institute of Geriatrics,General Hospital of Chinese PLA between January 2006 and January 2007.PARTICIPANTS:A total of 152 elderly Chinese Han people were selected from the Beijing Troop Cadre's Sanitarium.Among them,60 patients with late-onset Alzheimer's disease,with a mean age of (82±7) years (range 67-94 years) and disease course of (5.9±4.4) years,comprising 44 males with a mean age of (83±7) years and 16 females with a mean age of (78±7) years,were selected for the case group.An additional 92 healthy elderly subjects,with a mean of (76±9) years (range 60-94 years),comprising 76 males with a mean age of (77±9) years and 16 females with a mean age of (70±8) years,were selected for the control group.There were no significant differences in age and gender between the two groups (P>0.05).METHODS:DNA was extracted from peripheral blood leukocytes using routine phenol/chloroform methodology.Prion protein gene codon 129 polymorphism and ApoE polymorphism were measured using PCR-restriction fragment length polymorphism.The ApoEε allele was considered the standard for analyzing correlations between prion protein gene codon 129 polymorphism and late-onset Alzheimer's disease.MAIN OUTCOME MEASURES:Prion protein gene codon 129 distribution;correlation between genotypic frequency and allele frequency of prion protein gene codon 129 with Alzheimer

Varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. Varicocele is the most common cause of secondary male infertility. Nitric oxide (NO), which has a role on varicocele pathophysiology, is synthesized by endothelial nitric oxide synthase gene (NOS3). In our study, we aimed to explain the relationship between varicocele, three common NOS3 polymorphisms (T-786C, G894T, 4b/a), and NOS3 mRNA expression levels. We investigated NOS3 T-786C, G894T, and 4b/a polymorphisms in 102 patients with varicocele and 100 healthy controls. Twenty-four patients and 17 controls were chosen for expression studies based on polymorphism subgroupings. Subgroup 1 includes patients who have no minor allele polymorphisms, and subgroups 2, 3, and 4 have T-786C, G894T, and 4b/a polymorphisms, respectively. The 4b/a polymorphism demonstrated significantly elevated levels in both allele and genotype analysis in the control group compared to the patient group. The G894T polymorphism was statistically elevated for genotypic frequencies in the patient group compared to the control group, but this finding did not extend to allelic frequencies. There were no statistically significant differences in either the allelic or genotypic frequencies between patients and control groups for the T-786C polymorphism. When patient and control expression levels were compared without considering the subgroups, the NOS3 expression level was found to be statistically higher in the patient group. There were no statistically significant differences in the patient and control group expression levels when stratified by subgroup, nor was there any effect of the polymorphisms under study on expression levels. The 4b/a polymorphism may have a protective effect for varicocelem and G894T polymorphism may contribute to varicocele occurrence by lowering the level of NO. The higher NOS3 expression levels in the patient group may be a kind of dilator compensatory mechanism to protect vascular

Full Text Available Abstract Study objective The pathogenesis of chronic obstructive pulmonary disease (COPD is characterized by an interaction of environmental influences, particularly cigarette smoking, and genetic determinants. Given the global increase in COPD, research on the genomic variants that affect susceptibility to this complex disorder is reviving. In the present study, we investigated whether single nucleotide polymorphisms in 'a disinter-grin and metalloprotease' 33 (ADAM33 are associated with the development and course of COPD. Patients and design We genotyped 150 German COPD patients and 152 healthy controls for the presence of the F+1 and S_2 SNPs in ADAM 33 that lead to the base pair exchange G to A and C to G, respectively. To assess whether these genetic variants are influential in the course of COPD, we subdivided the cohort into two subgroups comprising 60 patients with a stable and 90 patients with an unstable course of disease. Results In ADAM33, the frequency of the F+1 A allele was 35.0% among stable and 43.9% among unstable COPD subjects, which was not significantly different from the 35.5% found in the controls (P = 0.92 and P = 0.07, respectively. The frequency of the S_2 mutant allele in subjects with a stable COPD was 23.3% (P = 0.32, in subjects with an unstable course 30.6% (P = 0.47. Conclusion The study shows that there is no significant difference in the distribution of the tested SNPs between subjects with and without COPD. Furthermore, these polymorphisms appear to have no consequences for the stability of the disease course.

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD).METHODS: Two hundred patients with Crohn's disease (CD), 186 ulcerative colitis (UC) patients, 434 parents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes,IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus,and 113G/A variant of the DLG5 gene were evaluated.Potential correlations with clinical sub-phenotypes were investigated.RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P ＜ 0.001).Homozygosis for both OCTN1/2 variants was more common in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an increased frequency of the TC haplotype (44.8% vs 38.3%in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was more frequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed.CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric onset of CD. Polymorphisms of CARD15, OCTN, and DLG5genes exert a weak influence on CD phenotype.

Aim: In this study, we examined parts of six growth genes (growth hormone [GH], melanocortin 4 receptor [MC4R], growth hormone receptor [GHR], phosphorglycerate mutase [PGAM], myostatin [MSTN], and fibroblast growth factor [FGF]) as specific primers for two rabbit lines (V-line, Alexandria) using nucleotide sequence analysis, to investigate association between detecting single nucleotide polymorphism (SNP) of these genes and body weight (BW) at market. Materials and Methods: Each line kits were grouped into high and low weight rabbits to identify DNA markers useful for association studies with high BW. DNA from blood samples of each group was extracted to amplify the six growth genes. SNP technique was used to study the associate polymorphism in the six growth genes and marketing BW (at 63 days) in the two rabbit lines. The purified polymerase chain reaction products were sequenced in those had the highest and lowest BW in each line. Results: Alignment of sequence data from each group revealed the following SNPs: At nucleotide 23 (A-C) and nucleotide 35 (T-G) in MC4R gene (sense mutation) of Alexandria and V-line high BW. Furthermore, we detected the following SNPs variation between the two lines: A SNP (T-C) at nucleotide 27 was identified by MC4R gene (sense mutation) and another one (A-C) at nucleotide 14 was identified by GHR gene (nonsense mutation) of Alexandria line. The results of individual BW at market (63 days) indicated that Alexandria rabbits had significantly higher BW compared with V-line rabbits. MC4R polymorphism showed significant association with high BW in rabbits. Conclusion: The results of polymorphism demonstrate the possibility to detect an association between BW in rabbits and the efficiency of the used primers to predict through the genetic specificity using the SNP of MC4R. PMID:28246458

Association of 13 single nucleotide polymorphisms (SNPs) of insulinase (IDE) gene with type 2 diabetes mellitus (T2D) in the Moscow population has been examined. Three polymorphic markers (rs7078413, rs7899603, and rs551266) associated with the risk of T2D development have been revealed. Allele and genotype frequency distribution for these three markers differed significantly only in the sample of females between T2D patients and control individuals, while only in case of rs7078413 SNP genotype frequencies varied significantly in the total population.

Full Text Available Objective(s:The aim of the study was to investigate the relationship between insulin resistance (IR and leptin (LEP genepolymorphisms in peritoneal dialysis (PD patients. Materials and Methods: From July 1, 2011 to August 1, 2011, patients who received chronic PD were chosen and divided into three groups (DM, high HOMR-IR, and low HOMR-IR. Two PCR products of LEP were sequenced and aligned and the distribution of polymorphisms was analyzed using χ2 analysis. In addition, serum leptin level, PD conditions, and biochemical parameters according to different genotype of G-2548A and A19G were statistically analyzed (P-value

Uncoupling proteins are mitochondrial membrane transporters, which regulate metabolic pathways of energy balance, and are associated with biological traits of animal body weight, resting metabolic rates and energy conversion. In this study, a region of the exons 3 and 4 of pig UCP2 gene was cloned and analyzed, and a new single nucleotide polymorphic site was detected by PCR-SSCP in five pig breeds. This newfound polymorphism results from a T to G substitution at the position of nucleotide 272, which is located in intron3.

Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 poly...

Cerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic...... protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p...

In leishmaniasis, cysteine protease b (cpb) multicopy genes have been extensively studied because of their implication in host-parasite interactions. In the Leishmania donovani complex, responsible for visceral leishmaniasis, a set of interesting polymorphisms has been revealed, such as copy sequence or expression according to the parasite's life stage. The single nucleotide polymorphisms observed among these copies could be related to clinical characteristics such as dermotropic versus viscerotropic status. CPB COOH-terminal extension (CTE) is mainly responsible for genetic variability among the copies and appears highly immunogenic. These results suggest that further study of the role of CPBs, especially CTE in clinical outcome, is warranted.

Full Text Available Abstract. Angiogenesis plays the major role in growth, progression and metastasis of different solid umors. Vascular endothelium growth factor (VEGF is a basic factor of angiogenesis regulation. The aim of present study was to evaluate possible correlations between C-2578A and C+936T VEGFА gene functional polymorphisms, and risk of breast cancer development. An association of -2578AA and -2578СС /+936СС VEGFA polymorphisms with incidence of breast cancer was revealed in our study. Distinct features of VEGFA genotype distribution were found for women with lymphogenic metastases and differences in menstrual status.

AIM:To investigate the associations between CDH1 genepolymorphisms and gastric cancer(GC) risk predisposition.METHODS:We analyzed four CDH1 polymorphisms(+54 T>C,-160 C>A,-616 G>C,-3159 T>C) in an Omani population,by extraction of genomic DNA from the peripheral blood of 192 patients with GC and 170 control participants and performed CDH1 genotyping using DNA sequencing.RESULTS:CDH1-160-AA genotype was associated with an increased risk of GC(OR = 3.6,95% CI:1.1-11.8)(P = 0.03).There was no significant asso...

Stimulation of PPARγ turns mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the PPARγ gene on BMD and fracture risk in two Danish cohorts and found opposing effects of certain SNPs and haplotypes in the two cohorts probably owing...... to environmental factors. INTRODUCTION: Stimulation of PPARγ causes development of mesenchymal stem cells to adipocytes instead of osteoblasts leading to decreased osteoblast number and BMD. The aim of this study was to examine the effect of PPARG polymorphisms on BMD and fracture risk in two Danish cohorts: AROS...

BACKGROUND—The vitamin D receptor (VDR) gene represents a strong positional candidate susceptibility gene for inflammatory bowel disease (IBD). The VDR gene maps to a region on chromosome 12 that has been shown to be linked to IBD by genome screening techniques. It is the cellular receptor for 1,25(OH)2 vitamin D3 (calcitriol) which has a wide range of different regulatory effects on the immune system. IBD is characterised by activation of the mucosal immune system. AIM—To determine if polymo...

OBJECTIVE: Adiponectin genepolymorphisms are associated with obesity, metabolic syndrome and type 2 diabetes (T2D). The study evaluated possible associations of +45T/G and -11391G/A adiponectin genepolymorphisms with body mass index (BMI), waist circumferences (WC), and blood pressure in diabetic and non-diabetic Iranians. METHODS: This cross-sectional study involved two groups of subjects: 243 diabetic patients and 173 non-diabetic subjects recruited from Rafsanjan city in the south-east of Iran. RESULTS: No significant association was found between +45T/G and -11391G/A adiponectin genepolymorphisms and systolic or diastolic blood pressure. However, male carriers of the TT genotype of +45T/G had a significantly higher mean BMI than male GG homozygotes (p = 0.018). Also, male carriers of the GG genotype of -11391G/A had significantly higher mean BMI than male GA or AA homozygotes (p = 0.041). Female carriers of the GG genotype of -11391G/A had significantly higher mean WC than female GA or AA homozygotes (p = 0.038). CONCLUSIONS: We observed a significantly higher BMI in women, and GA or AA carriers of -11391G/A polymorphism. Also, there was a significantly lower WC in females and GG carriers of +45T/G. These results point to a gender-specific impact of the studied genotypes on BMI and WC. PMID:21409316

Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical manifestations and target tissue damage. Currently, several genes have been associated with SLE susceptibility, including vitamin D receptor (VDR), which is a mediator of immune responses through the action of vitamin D. Polymorphisms in the VDR gene can impair the vitamin D (D3) function role, and since SLE patients show deficient D3 blood levels, it leads to a possible connection to the disease's onset. In our study we searched for an association between VDR polymorphisms and risk of developing SLE, as well as the disease's clinical manifestations. We enrolled 158 SLE patients and 190 Southeast Brazilian healthy controls, genotyped for five Tag single nucleotide polymorphisms (SNPs), covering most of the VDR gene region. We found an association between VDR SNPs and SLE for the following clinical manifestations: rs11168268 and cutaneous alterations (p=0.036), rs3890733 (p=0.003) rs3890733 and arthritis (p=0.001), rs2248098 and immunological alterations (p=0.040), rs4760648 and antibody anti-dsDNA (p=0.036). No association was reported between VDR polymorphisms and SLE susceptibility.

The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

Full Text Available The CB1 cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in energy balance control, stimulating appetite and increasing body weight in wasting syndromes. Different studies have investigated the relationship between polymorphisms of the cannabinoid receptor 1 (CNR1 gene and obesity with conflicting results. In the present study, we investigated the 1359G/A (rs1049353, 3813A/G (rs12720071 and 4895A/G (rs806368 polymorphisms in the CNR1 gene in a Brazilian population of European descent. To verify the association between these variants and obesity-related traits in this population, 756 individuals were genotyped by PCR-RFLP methods. The 4895G allele was associated with waist to hip ratio (WHR (P = 0.014; P = 0.042 after Bonferroni correction. An additive effect with the GAA haplotype was associated with WHR (P = 0.028, although this statistical significance disappeared after Bonferroni correction (P = 0.084. No significant association was observed between the genotypes of the 1359G/A and 3813A/G polymorphisms and any of the quantitative variables investigated. Our findings suggest that CNR1 genepolymorphism is associated with central obesity in this Brazilian population of European ancestry.

The DRB3 gene is an MHC class II gene that has a high degree of polymorphism with more than 100 alleles described in cattle. This variation contributes to differences among individuals in immune responsiveness and disease resistance. In this study, we searched for allelic variants in exon 2 of the DRB3 gene in 80 river buffaloes of three breeds in Brazil using a PCR-RFLP technique. The PCR product showed genetic polymorphism when digested with RsaI, PstI or HaeIII restriction enzymes. In total, 16 restriction patterns were identified: nine restriction patterns and 16 genotypes were found with RsaI; four restriction patterns and nine genotypes were found with HaeIII; and, three restriction patterns and four genotypes were found with PstI. Three RFLP patterns were exclusive to Jafarabadi buffaloes (RsaI-b, RsaI-c and RsaI-f) and three others were only observed in Mediterranean buffaloes (RsaI-g, RsaI-h and PstI-y). Jafarabadi buffaloes had a larger number of RFLP patterns than Mediterranean and Murrah breeds. The analysis showed that the DRB3 exon 2 was highly polymorphic, with the highest degree of polymorphism in Mediterranean buffaloes. This study provides the first assessment of allelic variation among three different buffalo breeds from Brazil and provides a basis for further investigations into the association between the DRB3 alleles and disease resistance.

Full Text Available The aim of this paper was to analyze the segregation of some polymorphisms in three genes (CAPN1, CAST and DGAT1 related to meat quality in the Lidia cattle breed and some of its main lineages. To that effect, 119 individuals from the Lidia breed were analyzed. Although the association between the polymorphisms and the phenotype has never been demonstrated in this breed, the absence of fixed genotypes for these polymorphisms in the studied population makes the Lidia cattle a good candidate to develop selection objectives. The clear differentiation among lineages for most of the genes studied reinforces the high reproductive isolation presented in the Lidia cattle as revealed by previous studies on the structure of the population within the Lidia breed using microsatellite markers. Considering both issues in the design of breeding schemes will be necessary to save the lineages and not to lose this valuable genetic resource. Finally, it would be necessary to carry out an in depth search for new polymorphisms in genes associated with meat quality and to perform needed association analyses between the SNPs segregating in Lidia cattle and traits of economic interest.

Full Text Available Biochemical polymorphism study is a method of determination of genetic variation. This variability could be a basis for selection and subsequent genetic improvement in farm animals. The polymorphism in the intron 1 of chicken growth hormone (cGH gene was investigated in the Iranian native fowls by using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP method. The genomic DNA was extracted from 217 samples (129 samples from the native fowls of Isfahan province and 88 samples from the native fowls of Mazandaran province by using modified salting out technique. The DNA fragment of the growth hormone gene with 776 bp was amplified by PCR using specific primers. Then the PCR products were digested with MspI restriction enzyme and analyzed on 2.5% agarose gel. The allelic frequency of intron 1 locus for A1, A2 and A3 alleles in Isfahan native fowls were 0.60, 0.21 and 0.19 and those in Mazandaran native fowls were 0.28, 0.05 and 0.67, respectively. The results of current study indicated that the intron 1 of cGH is polymorphic in Iranian native fowls and could be exploited as a candidate gene for marker-assisted selection for growth-related traits.

A number of studies have investigated the relationship between the PON1 genepolymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 genepolymorphisms and breast cancer risk. After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals. The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71-1.42). For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer.

Rho/Rho-kinase pathway plays a critical role in the regulation of cellular functions such as proliferation and migration. One of the possible theories of the development of ventricular septal defects is cell migration disorder. The aim of this study was to analyze the genotype distributions and allele frequencies for the ROCK2 gene Thr431Asn polymorphisms in the development of cardiac septal defects in a Turkish population. In this case-control study, 300 patients with cardiac defects (150 patients with ventricular and 150 patients with atrial septal defects) and control group (150 healthy control subjects) were investigated. A single-nucleotide polymorphism in ROCK2 gene Thr431Asn was analyzed by real-time PCR using a Light-Cycler. Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. These results suggest that there is no association of the ROCK2 gene Thr431Asn polymorphism with the development of cardiac septal defects in pediatric patients.

Full Text Available Abstract Background Major depressive disorder (MDD is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE has an important role in renin-angiotensin system (RAS and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D polymorphism of ACE gene. Objective The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolism-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 14C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C) metabolism; the interaction between polyunsaturated fatty acids (PUFA) and the 5G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the -1131T>C in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken. (Author) 31 refs.

Jun 11, 2014 ... Cows with genotype AA showed a lower milk protein percentage ... Quantitative traits in dairy cattle are controlled by a large number of genes and ..... Evaluation of marker-assisted selection through computer simulation.

Objective To identify single nucleotide polymorphisms (SNPs) of human CatSper gene, the mouse homologous gene product, which plays a crucial role in mouse male sterility.Methods We demonstrated a systematic screening of SNPs in coding regions and flanking intronic regions of human CatSper gene in a sample subset from a total 210 male individuals by DNA sequencing. Then we used PCR single-strand conformation polymorphism (SSCP) analysis to determine the allele frequencies of the possible SNPs among the whole 210 Chinese Han male individuals.Results Three SNPs, including two novels, were identified and their allele frequencies were determined in the 210 Chinese Han male individuals. These SNPs were assembled into large SNP database that promises to enable the dissection of the genetic basis of disease.

The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined...... by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06–2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21–2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability....... In conclusion, polymorphisms in these genes may be indicated as potential biomarkers for prostate cancer....

Objective To identify an interaction between the interleukin-1 receptor antagonist genepolymorphism and risk of Alzheimer's disease.Methods The study included 117 healthy controls, 85 patients with Alzheimer's disease in a Northeastern Chinese population of Han nationality. Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment,harbouring a variable number of short tandem nucleotide sequences. Amplification products were separated on a 2% agarose gel.Results The allele 2 frequency was 27% in healthy controls, and 21% in patients with Alzheimer's disease. Thus for allele 2 as well as for all other alleles, genotypes, or carriage rates, no significant differences compared with controls.Conclusions No association ofinterleukin-1 receptor antagonist genepolymorphism with Alzheimer's disease was identified in this population. It is also possible that the increased risk and disease modifying effects are caused by linkage disequilibrium with other genomic variants in other nearby genes.

Full Text Available Purpose of the work is to find the molecular-genetic markers of Pro12 Ala polymorphism of PPARG of hereditary predisposition to the manifestation of a high physical performance. During the work 122 athletes of different sports and 82 people who are not involved in sports were examined. The peculiarities of distribution of allele variants of PPARG gene in groups of athletes involved in different sports were obtained. It was found that a group of highly skilled athletes involved in sports with predominantly anaerobic nature of the energy PPARG Ala allele of the gene found in 11.1% more than the group of athletes involved in sports with mainly aerobic nature of the power supply. The existence of association between the Pro12 Ala polymorphism of PPARG gene and predisposition to various sports activities was established

Individual changes in dopamine-related genes influence prefrontal activity during cognitive-affective processes; however, the extent to which common genetic variations combine to influence prefrontal activity is unknown. We assessed catechol-O-methyltransferase (COMT) Val108/158Met (rs4680) and dopamine D2 receptor (DRD2) G-T (rs2283265) single nucleotide polymorphisms and functional magnetic resonance imaging during an emotional response inhibition test in 43 healthy adults and 27 people with schizophrenia to determine the extent to which COMT Val108/158Met and DRD2 G-T polymorphisms combine to influence prefrontal response to cognitive-affective challenges. We found an increased number of cognitive-deficit risk alleles in these two dopamine-regulating genes predict reduced prefrontal activation during response inhibition in healthy adults, mimicking schizophrenia-like prefrontal hypoactivity. Our study provides evidence that functionally related genes can combine to produce a disease-like endophenotype.

Full Text Available Background : Ischemic stroke is a frequent heterogeneous multifactorial disease. A number of genetic mutations and environmental factors have been implicated. A polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR has been reported to be associated with hyperhomocysteinemia a risk for atherosclerotic vascular diseases. Aim : A cross-sectional study was performed to determine the relationship between the genepolymorphism for MTHFR and ischemic stroke in type 2 diabetes mellitus. Materials and Methods : Of the 215 unrelated patients with type 2 diabetes mellitus recruited, 119 patients had ischemic stroke, Control group included 142 healthy subjects. The genotype of the subjects for the C677T polymorphism of MTHFR was analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP followed by HinfI digestion. Plasma total homocysteine (Hcy levels were measured using high-performance liquid chromatography (HPLC with fluorescence detection. Results : The genotype distribution did not differ between the control subjects and type 2 diabetic patients (P > 0.05. Plasma homocysteine levels were markedly higher in diabetic patients with TT genotype than those with CC or CT genotype (P > 0.05. Ischemic stroke was more frequently observed in type 2 diabetic patients with the TT genotype than in those with the CT and CC genotype (odds ratio=4.04, 95% CI=1.95-8.34, P=0.0036. Logistic regression analysis revealed that the C677T mutation of MTHFR gene was independently associated with ischemic stroke in type 2 diabetes. Conclusion : MTHFR C677T genepolymorphism associated with a predisposition to hyperhomocysteinemia could constitute a useful predictive marker for ischemic stroke in type 2 diabetic Chinese patients.

Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Genepolymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p=0.005 and p=0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p<0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p=0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).

Full Text Available OBJECTIVES:Asthma is a chronic inflammatory lung disease characterized by bronchial hyperresponsiveness and airflow obstruction. Genetic and oxidative stress factors, in addition to pulmonary and systemic inflammatory processes, play a pivotal role in the pathogenesis of asthma. The products of the multidrug resistance-1 gene protect lung tissue from oxidative stress. Here, we aimed to evaluate the association between the multidrug resistance-1 gene C>T polymorphism and asthma with regard to oxidative stress-related parameters of asthmatic patients.METHODS:Forty-five patients with asthma and 27 healthy age-matched controls were included in this study. Blood samples were collected in tubes with ethylenediaminetetraacetic acid. DNA was extracted from the blood samples. The multidrug resistance-1 genepolymorphism was detected by polymerase chain reaction and a subsequent enzyme digestion technique. The serum levels of total oxidant status and total antioxidant status were determined by the colorimetric measurement method.RESULTS:The heterozygous polymorphic genotype was the most frequent in both groups. A significant difference in the multidrug resistance-1 genotype frequencies between groups indicated an association of asthma with the TT genotype. A significant difference between groups was found for wild type homozygous participants and carriers of polymorphic allele participants. The frequency of the T allele was significantly higher in asthmatic patients. The increase in the oxidative stress index parameter was significant in the asthma group compared with the control group.CONCLUSIONS:The multidrug resistance-1 gene C/T polymorphism may be an underlying genetic risk factor for the development of asthma via oxidant-antioxidant imbalance, leading to increased oxidative stress.

Full Text Available Dirofilaria immitis, a filarial parasite, causes cardiopulmonary dirofilariasis in dogs, cats and wild canids. The macrocyclic lactone (ML class of drugs has been used to prevent heartworm infection. There is confirmed ML resistance in D. immitis and thus there is an urgent need to find new anthelmintics that could prevent and/or control the disease. Targeting ion channels of D. immitis for drug design has obvious advantages. These channels, present in the nematode nervous system, control movement, feeding, mating and respond to environmental cues which are necessary for survival of the parasite. Any new drug that targets these ion channels is likely to have a motility phenotype and should act to clear the worms from the host. Many of the successful anthelmintics in the past have targeted these ion channels and receptors. Knowledge about genetic variability of the ion channel and receptor genes should be useful information for drug design as receptor polymorphism may affect responses to a drug. Such information may also be useful for anticipation of possible resistance development. A total of 224 ion channel genes/subunits have been identified in the genome of D. immitis. Whole genome sequencing data of parasites from eight different geographical locations, four from ML-susceptible populations and the other four from ML-loss of efficacy (LOE populations, were used for polymorphism analysis. We identified 1762 single nucleotide polymorphic (SNP sites (1508 intronic and 126 exonic in these 224 ion channel genes/subunits with an overall polymorphic rate of 0.18%. Of the SNPs found in the exon regions, 129 of them caused a non-synonymous type of polymorphism. Fourteen of the exonic SNPs caused a change in predicted secondary structure. A few of the SNPs identified may have an effect on gene expression, function of the protein and resistance selection processes.

Full Text Available Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769 and two SNPs in the 3' UTR (rs3746544 and rs1051312 of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901 using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels.

Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed. We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.

Neuropeptide Y (NPY) gene has been shown to have a critical role in the regulation of satiety, reproduction, central endocrine and cardiovascular systems. Among the primary functions associated with NPY are its acute effects on feeding behavior and energy expenditure. The aim of this study is to evaluate the relationship between obesity and NPY genepolymorphisms in a South Indian Population. Three polymorphisms in NPY gene (Leu7Pro, Ser50Ser and A7735G) were analyzed in 263 individuals of an endogamous Kota population. On the basis of body mass index (BMI), they were divided into two groups. Associations were tested using logistic regression and haplotype analyses and linkage disequilibrium (LD). There was no evidence of deviation from Hardy-Weinberg equilibrium. Logistic regression analysis did not reveal significant association with obesity and NPY single-nucleotide polymorphisms (SNPs) in the present study. All three SNPs were in weak LD with low r (2) values. Haplotype analysis also did not yield significant association between NPY gene and obesity (global P=0.756). Our study did not validate the association between previously implicated SNPs in NPY gene and obesity in an Indian population. Population-specific validation of putative associations has far reaching implications for the future personal genomics medicine applications.

Background Genetic association studies on populations of European origin have identified the DCDC2 gene as a susceptibility locus for developmental dyslexia.Here,we sought to investigate the association of DCDC2 polymorphisms with developmental dyslexia in children of Han Chinese origin.Methods We undertook a case-control genetic association study on 76 dyslexic children and 79 non-dyslexic matched controls.We isolated DNA from oral mucosal cell samples and genotyped two DCDC2 coding-sequence single nucleotide polymorphisms,rs2274305 and rs6456593,in each sample using SNaPshot single nucleotide extension.We compared the allele and genotype frequencies between the groups using the X2 test and analyzed the relationship between dyslexia and the polymorphism at both loci using unconditional logistic regression.We also predicted haplotypes and compared their frequencies between the two groups.Results The differences in the genotype distribution and the allelic genes of the two single nucleotide luci of the DCDC2 gene,rs2274305 and rs6456593,between the two dyslexic and non-dyslexic groups were statistically meaningless (P ＞0.05).The differences in the haplotype distributions of the DCDC2 gene between the dyslexic and normal group were statistically meaningless (P ＞0.05).Conclusion The DCDC2 gene may not be a susceptibility factor for developmental dyslexia among the Han Chinese.However,methodological issues may have prevented the detection of oositive associations.

Goat's αS1-casein (CSN1S1) polymorphism has a significant effect on milk protein and lipid composition, which affects the nutritional quality and technological properties of milk. Moreover, this polymorphism has a large impact on the morphology of mammary epithelial cells. To explore the metabolic pathways modulated in relation to this polymorphism, we compared the mammary gene expression profiles of two groups of lactating goats carrying either two reference or two defective alleles, using a bovine oligonucleotide microarray representing 8379 genes. We identified 41 differentially expressed genes between the two genotype groups. In particular, we showed a downregulation of two key lipogenic genes encoding fatty acid synthase and glycerol-3-phosphate acyltransferase in agreement with the low fat concentration associated with CSN1S1 deficiency. In addition, this study highlights changes in the expression level of several genes known to influence membrane fluidity, cell-cell interaction or chromatin organization. Our results open up new fields of investigation on structural modifications associated with CSN1S1 deficiency that could affect mammary gland function.

Background Numerous studies have evaluated the association between interleukin-18 (IL-18) promoter gene-607C/A (rs1946518) polymorphism and tuberculosis (TB) risk.However,the results remain apparently conflicting.The aim of this study was to investigate whether IL-18-607C/A polymorphism is associated with susceptibility to TB.Methods Publications addressing the association between the IL-18-607C/A polymorphism and TB risk were selected from the Pubmed,Cochrane Library,Embase,CNKI and Wanfang databases.Data were extracted from the studies by two independent reviewers.Statistical analysis was performed using RevMan 5.0.25 and STATA 11.0 software.Results Eight case-control studies with a total of 1166 TB patients and 1734 controls were retrieved.Meta-analysis results showed significant association between IL-18-607C/A polymorphism and TB risk in all comparisons of the A allele versus C allele (OR=1.17,95％ Cl 1.05-1.30,P=0.004),AA versus CC (OR=1.43,95％ CI 1.14-1.81,P=0.002),CA+AA versus CC (OR=1.20,95％ C/ 1.01-1.42,P=0.04) and AA versus CA+CC (OR=1.30,95％ C/ 1.07-1.58,P=0.007).In subgroup analysis by nationality,a significant association between IL-18-607C/A polymorphism and TB risk in the comparisons of A versus C,CA+AA versus CC and AA versus CA+CC (OR=1.22,95％ C/ 1.07-1.38,P=0.002;OR=1.31,95％ C/ 1.06-1.61,P=0.01; OR=1.32,95％ C/ 1.07-1.63,P=0.01,respectively) were found in Chinese population but not in Indian and Iranian populations.Conclusion This study suggests that the-607C/A polymorphism of IL-18 gene would be a risk factor for TB,especially in Chinese population.To further evaluate gene-to-gene and gene-to-environment interactions on-607C/A polymorphism and tuberculosis risk,more studies with thousands of patients are required.

Objective To determine whether interleukin-1α and 1β genepolymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1β and rheumatoid arthritis (RA) motif gene. Methods IL-1 genepolymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1α-889 and IL-1β+3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1β2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data.Results There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and the controls. The β2/2 genotype of IL-1β was more common in female RA patients compared with controls (P=0.001). A lower carriage rate of IL-1β2 occurred in male RA patients (P=0.001). A higher carriage rate of IL-1α2 is associated with a higher ESR (P=0.008), HAQ score (P=0.03), and vit-D3 (P<0.001), but conversely a lower SJC (p=0.002), a lower RF (P=0.002) and a lower BMD at the lumbar spine (P=0.001). A higher frequency of IL-1α1 is associated with a lower CRP value (P=0.009). An increased IL-1β2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P<0.001), ESR (P<0.001) and pain score (P=0.001) and a higher BMD at the lumbar spine (P=0.007), lower vit-D3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time did not contribute to disease activity

Background: Senile cataract is the most common type of cataract characterized by gradual progressive thickening of the lens of the eye. Previously, many studies investigated the association between genetic polymorphism and senile cataract. Angiotensin-converting enzyme (ACE) I/D polymorphism is the potential risk factor for many eye-related diseases such as retinopathy and glaucoma. CYP46A1 enzyme converts cholesterol to 24S-hydroxycholesterol; human lens' membranes contain the highest cholesterol content. Defects in enzymes of cholesterol metabolism can be associated with cataracts. Hence, the present study was carried out to investigate the association of ACE and CYP46A1 genespolymorphism with senile cataract cases and controls. Materials and Methods: ACE (rs 4646994) and CYP46A1 (rs 754203) genespolymorphism in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. Results: This study included 103 senile cataract cases (55 were males and 48 were females) and 102 controls (53 were males and 49 were females). Mean age of cases in this study was 52.02 ± 12.11 years while in control group 53.74 ± 11.87 years. Frequencies of ACE ID, DD, and II genotypes in senile cataract cases were 64.07%, 4.85%, and 31.06% and controls were 61.76%, 26.47%, and 11.76%, respectively. The CYP46A1 gene CT, CC, and TT genotype frequencies were 48.54%, 8.73%, and 42.71% in senile cataract cases and 28.43%, 3.92%, and 67.64% in healthy controls, respectively. ACE DD and II genotypes (P < 0.001,P = 0.0008) and CYP46A1 CT and TT genotypes (P = 0.003,P = 0.0003) were significantly associated with senile cataract cases compared to the controls. Conclusion: Findings of this study suggest that ACE and CYP46A1 genespolymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genespolymorphism as a marker of susceptibility to senile cataract needs

Full Text Available Epidemiological studies have shown that E-selectin genepolymorphisms (A561C and C1839T may be associated with essential hypertension (EH, but the results are conflicting in different ethnic populations. Thus, we performed this meta-analysis to investigate a more authentic association between E-selectin genepolymorphisms and the risk of EH.We searched the relevant studies for the present meta-analysis from the following electronic databases: PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI. Odds ratios (OR with 95% confidence interval (CI were used to evaluate the strength of the association between E-selectin genepolymorphisms and EH susceptibility. The pooled ORs were performed for dominant model, allelic model and recessive model. The publication bias was examined by Begg's funnel plots and Egger's test.A total of eleven studies met the inclusion criteria. All studies came from Asians. Ten studies (12 cohorts evaluated the A561C polymorphism and EH risk, including 2,813 cases and 2,817 controls. The pooled OR was 2.280 (95%CI: 1.893-2.748, P<0.001 in dominant model, 5.284 (95%CI: 2.679-10.420, P<0.001 in recessive model and 2.359 (95%CI: 1.981-2.808, P = 0.001 in allelic model. Four studies (six cohorts evaluated C1839T polymorphism and EH risk, including 1,700 cases and 1,681 controls. The pooled OR was 0.785 (95%CI: 0.627-0.983, P = 0.035 in dominant model, 1.250 (95%CI: 0.336-4.652, P = 0.739 in recessive model and 0.805 (95%CI: 0.649-0.999, P = 0.049 in allelic model.The current meta-analysis concludes that the C allele of E-selectin A561C genepolymorphism might increase the EH risk in Asian population, whereas the T allele of E-selectin C1839T genepolymorphism might decrease the EH risk.

To test the hypothesis that analyses of drug targets for polymorphism will help to establish gene-based information for the treatment of cancer patients, we investigated the functional single-nucleotide polymorphisms in the human cytidine deaminase (HDCA) gene. The cDNAs from 52 leukaemia/lymphoma samples and 169 control blood samples were direct-sequenced and analysed for the polymorphisms. Three different polymorphisms (A79C, G208A and T435C) were identified in the coding region of the HDCA gene and displayed allelic frequencies of 20.1%, 4.3% and 70.1%, respectively. No association with susceptibility to disease was observed. A novel polymorphism, G208A produced an alanine to threonine substitution (A70T) within the conserved catalytic domain. By introduction of the polymorphic HCDA genes into the yeast CDA-null mutants, the HCDA-70T showed 40% and 32% activity of prototype for cytidine and ara-C substrates, respectively (P HCDA-70T was 757 +/- 33 micromol and was significantly lower (P < 0.01) than that of prototype (941 +/- 58 micromol). This study demonstrated a population characterized with 208A genotype for, which potentially leads one more sensitive to ara-C treatment than prototype. Accumulation of polymorphisms in the genes responsible for drug metabolism and determination of polymorphism-induced biological variations could provide the additional therapeutic strategies in risk-stratified protocols for the treatment of childhood malignancies.

Full Text Available Objective: to study the distribution of the genotypes of the vascular endothelial growth factor (VEGF gene and their combinations with those of other cytokines among patients with rheumatoid arthritis (RA and healthy individuals. Subjects and methods. 509 Europeoid women from the eastern regions of Russia, including 374 healthy individuals aged 23-64 years and 135 RA patients aged 27-66 years, were examined. The single nucleotide polymorphism in the promoter region of the genes of VEGC -2578 C/A, tumor necrosis factor-а (TNF-а -863 C/A, TNF-а -308 G/A, TNF-а -238 G/A, and interleukin (IL 1β -31 С/T, IL4 -590 С/T, IL6-174 G/C, IL10-1082 G/A, and IL10-592А/С was studied by restriction fragment length polymorphism analysis. Results. Analysis of the frequency of the genotypes of VEGF in combination with other genotypes has revealed a number of highly significant genetic differences between the groups of healthy individuals and RA patients. Among the combined genetic signs (CGS, whose frequency is significantly increased in RA, there is a predominance of heterozygous CA genotypes at the polymorphic position of VEGF -2578 C/A. Among the CGS positively associated with RA, which include homozygous VEGF -2578 variants, there is a preponderance of AA genotypes whereas all 100% of the homozygous genotypes, whose frequency is significantly decreased in RA, correspond to the variant of СС. The CGS whose frequency is altered in RA along with VEGF genotypes most commonly include the genotypes of IL1ß, IL4, IL10, IL6, and TNF-а. Conclusion. The pathogenesis of RA calls for comprehensive investigation of the role of the angiogenesis and inflammation regulation genes.

Full Text Available Abstract Objective The aim of this study is to investigate the association between two polymorphisms of endothelial nitric oxide synthase (NOS3 and suicide attempts. Methods We genotyped 186 suicide attempters and 420 unrelated healthy controls. The following polymorphisms were analysed: T-786C and 27-bp repeat in intron 4. Results No significant differences were found in genotype or in allelic distribution of the aforesaid polymorphisms. There were also no differences in the genotype distribution or allelic frequencies when separately assessing males and females or impulsive and non-impulsive attempters and normal controls. Estimated haplotype frequencies were similar in both groups. Conclusion Our data do not support the hypothesis that genetically determined changes in the NOS3 gene confer increased susceptibility for suicidal behavior.

Full Text Available Asthma is a chronic inflammatory disorder delineated by a heightened immunological response due to environmental or genetic factors. Single nucleotide polymorphism studies have shown that FOXO3a plays a pivotal role in maintaining immunoregulation. Polymorphism in FOXO3a has been linked to inflammatory diseases such as chronic obstructive pulmonary disease (COPD, Rheumatoid Arthritis, and Crohn’s disease suggesting that FOXO3a may be associated with asthma. Airway inflammation in asthma is characterized by activation of T helper type 2 (Th2 T cells and Foxo family members are reported to play critical roles in the suppression of T cell activation. Thus this study was undertaken to investigate an association between single nucleotide polymorphism of the FOXO3a (rs13217795, C>T transition gene and asthma in Indian population. To our knowledge we are the first ones reporting an association between FOXO3a and asthma.

Full Text Available SUMMARY. Background: The function of the Klotho gene, originally identified by insertional mutagenesis in mice, is to suppress multiple aging phenotypes. It has been shown that a mutant Klotho gene is associated with pulmonary emphysema in mice. The aims of this study were to detect Klotho genepolymorphisms (-395G>A SNP and to identify their possible relationships with clinical findings in patients with chronic obstructive pulmonary disease (COPD. Methods: In 167 patients with COPD -395G>A SNP of the Klotho gene was genotyped by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP coupled with sequencing. The possible relationship was explored of -395G>A SNP with clinical findings such as lung function parameters, staging according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD, and body mass index (BMI. Results: Of the 167patients with COPD, 99 (59.3% presented the wild type -395G allele, 62 (37.1% were heterozygotes (–395GA allele, and 6 (3.6% presented the non-wild type–395A allele. In these COPD patients there was an association between Klotho genotypes and BMI (p=0.025. No association was found between Klotho genepolymorphism and disease severity, assessed by spirometry, arterial blood gases and GOLD stage. Conclusion: Klotho -395G>A polymorphisms are detected in patients with COPD and are associated with BMI, but not with various parameters of disease severity. This may suggest a possible metabolic pathway in the implication of Klotho deficient gene in the pathophysiology of emphysema in COPD patients. Pneumon 2010, 23(4:348-354.

Full Text Available Rodrigo Augusto da Silva,1 André Luis Shinohara,2 Denise Carleto Andia,1 Ariadne Letra,3 Regina Célia Peres,1 Ana Paula de Souza11Department of Morphology, Piracicaba Dental School, State University of Campinas, 2Oral Biology Program, Bauru Dental School, State University of São Paulo, São Paulo, Brazil; 3Department of Endodontics and Center for Craniofacial Research, School of Dentistry, University of Texas Health Science Center, Houston, TX, USAAbstract: Single nucleotide polymorphisms are genome variations that can be used as population-specific markers to infer genetic background and population origin. The Brazilian population is highly admixed due to immigration from several other populations. In particular, the state of São Paulo is recognized for the presence of Japanese individuals who seem likely to have contributed to a substantial proportion of ancestry in the modern Brazilian population. In the present study, we analyzed allele and genotype frequencies and associations of the –418G>C (rs8179090 single nucleotide polymorphism in the TIMP2 gene promoter in Brazilian and Japanese subjects, as well as in Japanese descendants from southeastern Brazil. The allele and genotype frequency analyses among groups demonstrated statistical significance (PC single nucleotide polymorphism of the TIMP2 gene, have a high probability of being Japanese or Japanese descendants. In addition to other genetic polymorphisms, the −418G>C TIMP2 polymorphism could be a population marker to assist in predicting Japanese ancestry, both in Japanese individuals and in admixed populations.Keywords: Brazilian, Japanese, polymorphism, allele, TIMP2

Full Text Available Primary immune thrombocytopenia (ITP is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP (C46359T in DNA methyltransferase 3B (DNMT3B gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra intron-2 in 32 children (17 boys with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94. In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50. Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

Full Text Available Hypertrophic cardiomyopathy (HCMP is a genetically determined myocardial disease, characterized by massive hypertrophy of the myocardium of the left and/or (rarely the right ventricle, often associated with obstruction of the left ventricular outflow tract and diastolic dysfunction. The course of disease can be complicated by development of various cardiac arrhythmias. It was reported that severity of HCMP course depends at certain degree on polymorphism of candidate genes, including genes of the renin angiotensin system (RAS. Influence of RAS genespolymorphism on the frequency and character of cardiac arrhythmias in childhood is almost not studied. Aim: to determine the influence of RAS genespolymorphism on the prevalence and structure of cardiac arrhythmias in children with HCMP. Patients and methods: analysis of influence of RAS genespolymorphism on the prevalence and structure of cardiac arrhythmias was performed in 32 children with HCMP. All the patients were carried out ECG, cardiac ultrasound and ECG Holter monitoring. Polymorphism of the RAS genes (renin gene (REN G83A, angiotensinogen gene (AGT M235T, angiotensin-converting enzyme gene (ACE I/D, angiotensin II receptor type 1 gene (AGTR1 A1166C. Results: in patients with HCMP was established a higher frequency of TT-genotype and T-alleles of angiotensinogen gene than in comparison group. In homozygous patients with T-allele of angiotensinogen gene ventricular arrhythmia was found reliably more often than in patients with MT- and MM-genotypes, which suggested that M235T polymorphism of angiotensinogen gene influenced on intensity of ventricular arrhythmias in children with HCMP. Conclusions: in children with HCMP and cardiac arrhythmias analysis of M235T polymorphism of angiotensinogen gene can be used as an additional criterion for revealing of patients with high risk of arrhythmic complications and for development of preventative measures.

Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels.

Full Text Available Coronary heart disease (CHD is a major cause of mortality. Morphological substrate of CHD in most cases is atherosclerosis, which is based on structural genespolymorphism eNOS and AGTR2. The aim of the study was to study the prevalence of eNOS and AGTR2 genes in patients with coronary artery disease and the association of these genes with coronary heart disease. The study involved 187 patients aged 36 to 86 years (62,2±11,2 with different forms of CHD: stable and unstable angina, myocardial infarction and 45 people without CHD. Determination of genepolymorphisms was performed by real-time PCR analyzer of nucleic acids IQ 5 Bio-Rad. Statistical analysis was performed using Statistica 10.0. The study revealed a significant difference between the incidence of homozygous AA allelic variant gene AGTR2 group of patients with myocardial infarction and the comparison group; polymorphic variant AA AGTR2 gene is associated with earlier onset of coronary artery disease; It found that carriers of the polymorphic variant gene GA AGTR2 beginning statistically CHD occurred significantly later than in carriers of alleles GG and AA; age CHD debut TT allele carriers of the eNOS gene is associated with an earlier onset of the disease and statistically significantly different from the age of first CHD in carriers of alleles of polymorphic variants of GG and GT; revealed a positive correlation between the polymorphic allele AGTR2 gene with the presence of arterial hypertension in patients with coronary artery disease; It determined that the T allele carriers of the polymorphicgene eNOS is associated more early onset of hypertension, found the association of the polymorphic allele gene AGTR2 the need to use higher doses of ACE inhibitor — perindopril.

Full Text Available Background & objectives: Association between polymorphisms in the natural resistance associated macrophage protein 1 (NRAMP1 gene and susceptibility to cutaneous leishmaniasis (CL has been demonstrated worldwide; however, the reported results were inconsistent. This study aimed to determine the association of NRAMP1 variants with susceptibility to CL infection and patients′ response to treatment in Isfahan province of Iran. Methods: Peripheral blood samples were collected from 150 patients with CL and 136 healthy controls. The CL patients were treated with intralesional injection of meglumine antimoniate. The polymorphic variants at NRAMP1 (A318V and D543N were analyzed using PCR-RFLP. The chi-square test and Fisher′s exact test were used to compare frequencies of alleles and genotypes of polymorphisms between patient and healthy control populations. Results: There was a statistically significant difference in the D543N (rs17235409 polymorphism between the CL patients and healthy controls (p=0.008. However, no significant association was detected for A318V (rs201565523 polymorphism between groups (p=0.26. In addition, there was a lack of association between D543N and A318V genotypes with response to treatment (p=0.54 and p=0.31, respectively. Interpretation & conclusion: The results indicated that genetic variations of D543N (rs17235409 might be associated with susceptibility to CL infection. These data may be used for detection of sensitive individuals and prevention of CL in endemic areas.

The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this genepolymorphism interacts with BMI in the risk of ischemic stroke.

Sodium channel Na(V)1.7, encoded by the SCN9A gene, is preferentially expressed in nociceptive primary sensory neurons, where it amplifies small depolarizations. In studies on a family with inherited erythromelalgia associated with Na(V)1.7 gain-of-function mutation A863P, we identified a nonsynonymous single-nucleotide polymorphism within SCN9A in the affected proband and several unaffected family members; this polymorphism (c. 3448C&T, Single Nucleotide Polymorphisms database rs6746030, which produces the amino acid substitution R1150W in human Na(V)1.7 [hNa(V)1.7]) is present in 1.1 to 12.7% of control chromosomes, depending on ethnicity. In this study, we examined the effect of the R1150W substitution on function of the hNa(V)1.7 channel, and on the firing of dorsal root ganglion (DRG) neurons in which this channel is normally expressed. We show that this polymorphism depolarizes activation (7.9-11mV in different assays). Current-clamp analysis shows that the 1150W allele depolarizes (6mV) resting membrane potential and increases ( approximately 2-fold) the firing frequency in response to depolarization in DRG neurons in which it is present. Our results suggest that polymorphisms in the Na(V)1.7 channel may influence susceptibility to pain.

AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n =162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment len...

Growth differentiation factor 9 (GDF9) belongs to the transforming growth factor β superfamily and plays a critical role in ovarian follicular development and ovulation rate. We examined the bovine GDF9 genepolymorphism and analyzed its association with superovulation performance. Based on the sequence of the bovine GDF9 gene, six pairs of primers were designed to detect single nucleotide polymorphisms of two exons and intron 1 of GDF9 using polymerase chain reaction-single-strand conformation polymorphism. Only the products amplified by primer 3-1 displayed polymorphisms. Sequencing revealed two mutations of A485T and A625T in intron 1 of the GDF9 gene in 171 Chinese Holstein cows treated for superovulation. Association analysis showed that these two single nucleotide polymorphisms of A485T and A625T had significant effects on the number of transferable embryos (P superovulation traits in Chinese Holstein cows.

Objective To investigate the association between nicotinamide N-methyltransferase(NNMT)gene rs694539 variant and non-alcoholic steatohepatitis(NASH).Methods A total of 76 NASH patients who visited or were hospitalized in our hospital from January2010 to June 2013,as well as 160 healthy volunteers matched with the patients for Face,age,and sex,

By amplifying the melanocortin type 1 receptor from the woolly mammoth, we can report the complete nucleotide sequence of a nuclear-encoded gene from an extinct species. We found two alleles and show that one allele produces a functional protein whereas the other one encodes a protein with strongly...

The mode of inheritance of the male sterility trait is crucial for understanding the evolutionary dynamics of the sexual system gynodioecy, which is the co-occurrence of female and hermaphrodite plants in natural populations. Both cytoplasmic (CMS) and nuclear (restorer) genes are known to be involv

Apr 25, 2016 ... genes on treatment induced viral clearance in HCV infected Egyptian .... shown to influence TNF-a expression [11]. Interferon gamma ... has been carried out in accordance with The Code of Ethics of the World ... Molecular testing. Genomic DNA ..... Our findings could be explained on the basis that genetic.

The importance of milk proteins and the positive effect of administration of growth hormone (GH) on milk production, and the presence in some dairy cattle lines of greater GH concentrations prompted us to examine the presence of restriction fragment length polymorphism at the GH gene using the restriction enzyme TaqI and to investigate associations between this polymorphism in Simmental cows and bulls, as well as milk protein variants in Simmental cows, and milk production traits. Blood and milk were sampled from 279 Italian Simmental cows and semen was collected from 148 bulls of the same breed. Two fragment bands, denoted A and B, of 6200 and 5200 bp respectively, were examined and three patterns, AA, AB and BB, were found in both animal samples. All variants previously reported in other studies, for kappa, beta, and alpha s1-caseins, and beta-lactoglobulin, were found in the cows' samples. For the cows' samples, a BLUP (Best Linear Unbiased Predictor) analysis of results was performed using a REML (Restricted Maximum Likelihood) program and known heritabilities, whereas for bulls we have performed a General Linear Model analysis. The effect of GH genepolymorphism, using TaqI restriction enzyme, on milk production traits was not significant, but bulls of BB pattern had a higher breeding value for milk yield than AA bulls (P casein genotypic effects, cows of AB genotype gave milk with 1.53 +/- 0.70 g/kg less fat than cows of AA genotype. In addition, breeding values for milk protein content were significantly higher in BB bulls, with 0.87 +/- 0.32 and 0.71 +/- 0.34 g/kg more milk protein than AA and AB bulls respectively. Thus, our results revealed a GH genepolymorphism and indicated significant effects of milk protein polymorphisms on milk production traits in the Italian Simmental breed.

Metabolism is an essential factor in the clearance of many drugs and as such plays a major role in the establishment of dosage regimens and withdrawal times. CYP2D6, the human orthologue to equine CYP2D50, is a drug-metabolizing enzyme that is highly polymorphic in humans leading to widely differing levels of metabolic activity. As CYP2D6 is highly polymorphic, in this study it was hypothesized that the gene coding for the equine orthologue, CYP2D50, may also be prone to polymorphism. Blood samples were collected from 150 horses, the CYP2D50 gene was cloned and sequenced; and full-length sequences were analyzed for single nucleotide polymorphisms (SNPs), deletions, or insertions. Pharmacokinetic data were collected from a subset of horses following the administration of a single oral dose of tramadol and probit analysis used to calculate metabolic ratios. Prior to drug administration, the ability of recombinant CYP2D50 to metabolize tramadol to O-desmethyltramadol was confirmed. Sequencing of CYP2D50 identified 126 exonic SNPs, with 31 of those appearing in multiple horses. Oral administration of tramadol to a subset of these horses revealed variable metabolic ratios (tramadol: O-desmethyltramadol) in individual horses and separation into three metabolic groups. While a limited number of horses of primarily a single breed were studied, the variabili